妊娠晚期母鼠脱水对胎儿及子代RAS的影响
|
摘要
研究背景:妊娠期多种原因如过度活动、发热、出血、呕吐及腹泻等均可造成孕妇机体脱水。脱水影响机体体液中水和电解质平衡,导致细胞内外失水。肾素血管紧张素系统(renin-angiotensin system, RAS)是调控体液平衡的重要内分泌系统,在调节机体心血管活动、神经内分泌、饮水饮盐行为等方面均起着重要作用。大量研究表明机体脱水可导致体液失衡及影响RAS,但有关妊娠期脱水对胎儿RAS及心脏、肾脏发育的影响尚不清楚。
Barker理论是目前国际上有关胎源性疾病的研究热点,大量流行病学及实验证据表明:宫内应激所导致“印迹”效应可“程序化”影响成年后心血管疾病(如高血压等)的发生,并发现RAS在高血压发病过程中起重要作用。然而,妊娠期母鼠脱水是否对成年子代的RAS产生印迹效应,是否影响子代RAS对体液平衡及心血管功能的调控,目前国内外尚未见报道。因此,本实验研究妊娠晚期母鼠脱水对胎鼠RAS和心脏、肾脏发育的影响,并研究脱水对成年子代大鼠RAS的印迹效应及其功能的影响。
第一部分妊娠晚期母鼠脱水对胎儿及其RAS发育的影响
目的:妊娠晚期母鼠脱水对胎儿的调控因素RAS及心脏、肾脏发育的影响。
方法:妊娠晚期母鼠脱水三天后,称量胎鼠体重、心重、肾重及其干重;血气分析仪检测母、胎鼠的血气指标和电解质,用渗透压仪检测血浆渗透压;用放射免疫法检测母、胎鼠血液中血管紧张素(angiotension, Ang)Ⅰ、AngⅡ、血管加压素(vasopressin,VP)和醛固酮(aldosterone,ALD)的浓度;用透射电镜方法检测胎鼠心、肾脏组织超微结构,并用激光多谱勒检测肾脏表面血流;用western blot和荧光定量PCR的方法检测胎鼠心脏、肾脏中血管紧张素受体(ATR)的蛋白和mRNA水平,并检测胎鼠肝脏中血管紧张素原(angiotensinogen, ATG)的mRNA水平。
结果:妊娠晚期母鼠脱水可使胎鼠体重、心脏和肾脏的重量明显降低,胎鼠血钠、红细胞压积及血浆渗透压增加,胎鼠血液中AngI、AngⅡ、VP和ALD的浓度明显增加,及肝脏中ATG的mRNA水平显著增加。妊娠晚期脱水可导致胎鼠心脏及肾脏超微结构的改变,明显增加胎鼠心脏中AT2R的mRNA和蛋白水平,但不影响AT1aR及AT1bR的mRNA和AT1R的蛋白水平;可明显增加胎鼠肾脏中AT1R与AT2R的mRNA和蛋白水平,并减少肾血流量。
结论:妊娠晚期脱水可明显改变胎鼠体内的RAS水平,并影响胎鼠心脏和肾脏的发育。
第二部分妊娠晚期母鼠脱水对成年子代RAS的“印迹”效应及其功能的影响
目的:研究妊娠晚期母鼠脱水对成年子代大鼠体内RAS水平的影响及其“印迹”效应,并研究妊娠晚期母鼠脱水对成年子代大鼠RAS调控体液平衡及心血管系统功能的影响。
方法:用妊娠晚期母鼠脱水组及对照组成年子代,检测子代大鼠体重、心脏和肾脏重量。在基础状态下,用血气分析仪检测成年子代大鼠血气指标和电解质,用渗透压仪检测血浆渗透压;用放射免疫法检测血液中AngI、AngⅡ、VP和ALD的浓度;检测成年子代大鼠心血管系统对PD123319、Losartan及AngII的应答;检测离体胸主动脉及肠系膜动脉对血管舒缩物质的反应;用western blot和荧光定量PCR的方法检测心脏及肾脏中AT1R和AT2R的蛋白和mRNA水平,并检测肝脏中ATG的mRNA水平。在脱水应激下,检测成年子代大鼠体内RAS组分的浓度,并检测脱水对成年子代大鼠体液平衡、心血管系统及饮水饮盐行为的影响。
结果:妊娠晚期母鼠脱水组雌、雄性成年子代大鼠的体重、心脏及肾脏的重量、血气指标及电解质、血液中AngI、AngⅡ、VP和ALD的浓度与对照组比较无差异,但脱水组成年子代大鼠肝脏中ATG mRNA水平及心脏、肾脏中AT1R与AT2R的mRNA和蛋白水平均明显不同于对照组。与对照组比较,脱水组雄性成年子代大鼠对AngⅡ、Losartan及PD123319的反应均明显增强,而雌性子代无差异性,但雌、雄性成年子代大鼠的压力反射敏感性均明显降低。脱水组成年子代大鼠的胸主动脉及肠系膜动脉对AngⅡ的收缩血管反应均明显增强。成年期脱水48h后,脱水组的雌、雄性成年子代鼠血气指标及电解质与对照组比较无差异性,但血浆中AngⅡ、VP和ALD的浓度明显高于对照组,饮盐量和血压也明显升高。
结论:妊娠晚期母鼠脱水对成年子代大鼠的RAS有“印迹”效应。脱水组雌、雄性成年子代大鼠对心血管系统的调控存在性别差异,压力反射敏感性降低可能是子代心血管系统应答“程序化”效应的共同机制。脱水组成年子代大鼠的血管对AngⅡ升高血压的敏感性增强,提示其发生高血压等心血管疾病的危险性明显升高。脱水组成年子代大鼠在脱水刺激时,AngⅡ、ALD及VP浓度升高更明显,这与饮盐量及血压的显著增加可能相关,表现为患高血压等心血管疾病的“易感性”提高。
第三部分妊娠晚期母鼠脱水对雄性成年子代大鼠心脏和肾脏蛋白质组影响的初探
目的:妊娠晚期母鼠脱水对雄性成年子代大鼠心脏和肾脏蛋白质组表达影响。
方法:采用双向电泳技术检测对照组及脱水组雄性成年子代大鼠心脏和肾脏中蛋白质组表达的差异。
结果:雄性成年子代大鼠心脏和肾脏组织中蛋白质分布模式在对照组和实验组之间基本一致。对照组和实验组心脏中获得的平均蛋白质斑点数分别为603±25及577±32个,差异点数为33个;而肾脏中平均蛋白质斑点数分别为975±30及1107±42个,差异点数为38个。
结论:初步建立了分辨率较高、重复性较好的正常和脱水组成年子代大鼠心脏与肾脏中总蛋白质双向电泳图谱。妊娠晚期母鼠脱水影响雄性成年子代大鼠心脏和肾脏中蛋白质组的表达。
Background: Women may face mild to severe dehydration due to exercise, fever, hemorrhage, vomiting, and diarrhea during pregnancy. Water deprivation (WD) is a potent stimulation to affect body fluid balance, and can lead to both extracellular and intracellular dehydration. Renin-angiotensin system (RAS), as an endocrine system, plays a role in regulating body fluid balance, cardiovascular system, neuroendocrine activity, and water and salt intake. A lot of evidence suggests that WD could induce changes in body fluid balance and RAS components in adults. However, it is largely unknown of effects of WD during pregnancy on the development of fetal RAS, and of the heart and kidney.
Barker theory hypothesizes diseases in fetal origins. There is now a body of substantial epidemiological and experimental evidence showing that intrauterine stress may program cardiovascular diseases such as hypertension in late life. Previous studies suggested that the RAS may play a critical role in pathophysiological progress of hypertension induced by adverse environment during fetal development. It is unknown whether exposure to prenatal WD can affect the RAS in its regulation of body fluid balance and cardiovascular system in the offspring. Hence, this project studies the effect of maternal WD during late term on the development of RAS, heart, kidney in both fetuses and offspring.
PART 1 Effects of maternal WD during late gestation on development of fetus and fetal RAS
Objective: To determine the development of the RAS, heart and kidney of the fetus exposure to WD at late term.
Methods: After three days of maternal WD, fetal body, heart, and kidney were weighted, and fetal blood gases and electrolytes were determined with a Nova analyzer, plasma osmolality was determined with an advanced digmatic osmometer. Both fetal and maternal plasma angiotensin (Ang)Ⅰ, AngⅡ, vasopressin (VP) and aldosterone (ALD) concentrations were measured by radioimmunoassay. The ultrastructures of fetal heart and kidney were detected by a transmission electron microscope and the renal blood flow was detected by a Laser Doppler. Protein and mRNA of AngⅡreceptors (ATR) in the fetal heart and kidney were determined with western-blot or real-time PCR, and ATG mRNA in the fetal liver was also determined.
Results: Prenatal exposure to WD at late term significantly decreased weight of the fetal body, heart and kidney, and increased fetal plasma Na+, hematocrit and osmolality. Fetal liver ATG mRNA, plasma AngⅠ, AngⅡ, VP, and ALD concentrations were also increased following WD. Maternal WD during late gestation changed the ultrastructures in the fetal heart and kidney, and altered the expression of both protein and mRNA of ATR in the fetal kidney and heart. Fetal renal blood flow was reduced.
Conclusion: Three days of maternal WD during late gestation significantly changed the concentrations of fetal RAS components, and affected the development of fetal heart and kidney.
PART 2 Imprinting effect and function of RAS of adult offspring exposure to maternal WD during late gestation
Objective: To determine the effect of maternal WD during late gestation on the RAS and its roles in regulation of body fluids and cardiovascular system in offspring. Methods: The offspring in both the control and WD groups were used. The adult offspring body, heart, and kidney were weighted. Blood gases and electrolytes were determined with a Nova analyzer, plasma osmolality was determined with an advanced digmatic osmometer, plasma AngⅠ, AngⅡ, VP, and ALD concentrations were measured by radioimmunoassay. Cardiovascular responses to intravenous injection of PD, losartan, and AngⅡ, and contractility of the thoracic aorta and mesenteric artery were determined. Protein and mRNA of ATR were measured with western blot and real-time PCR in both the heart and kidney of offspring, and ATG mRNA in fetal liver was also determined. The effect of WD on the RAS, body fluid balance, cardiovascular system, and both salt and water intake, offspring was determined.
Results: Maternal WD during late gestation did not change the weights of body, heart and kidney, the blood gases and electrolytes, the concentrations of plasma AngⅠ, AngⅡ, VP and ALD in adult offspring, but maternal WD during late gestation significantly changed the ATG mRNA levels in liver, and both ATR mRNA and proteins in both heart and kidney in adult offspring. Cardiovascular responses to injection of PD, losartan and AngⅡwere notably enhanced in male not female adult offspring in WD group compared to control, but baroreflex sensitivity was notably attenuated in both male and female offspring. Compared to control, the ability of both thoracic aorta and mesenteric artery to vasoconstriction to AngⅡwas enhanced in adult offspring of WD group. After 48h of WD again, blood gases and electrolytes had no difference in adult offsprings between control and WD group, but the concentrations of plasma AngⅡ, VP and ALD, salt intake and blood pressure were significantly elevated in adult offsprings in WD group than those of control.
Conclusion: Maternal WD during late gestation showed chronic influence on the RAS in the offspring. Cardiovascular responses to the stimulation following exposure to prenatal WD showed difference that was gender-dependent. The decrease of baroreflex sensitivity may be the mechanism for changes in the cardiovascular responses. Blood pressure and vasoconstriction to AngⅡwere significantly increased in the adult offspring exposure to prenatal WD. Response to stimulation, plasma AngⅡ, VP, and ALD concentrations were higher in the offspring exposure to prenatal WD than in the control, associated with an increase of salt intake. The data indicate an increase of risks for cardiovascular diseases such as hypertension in the adult offspring exposed to maternal WD during late gestation.
PART 3 Effects of maternal WD during late gestation on expression of proteome in the heart and kidney of the offspring
Objective: To determine the expression of proteome in both the heart and kidney in the adult male offspring exposure to maternal WD during late gestation.
Methods: Two dimensional electrophoresis (2-DE) was used to detect differences of proteome expression between the control and WD group in the heart and kidney of the adult male offspring.
Results: The basic distributions of total proteins were similar in both the heart and kidney in offsprings between the control and WD groups. The numbers of total proteins were 603±25 and 577±32 in the heart between the control and WD groups, in which thirty-three differential protein spots were identified. Total proteins were 975±30 and 1107±42 in the kidney between the control and WD groups, in which thirty-eight differential protein spots were identified.
Conclusion: 2-DE profiles with high resolution and reproducibility of total proteins were established in both the heart and kidney between the control and WD groups, and the expressions of differential proteins were found.
Barker理论是目前国际上有关胎源性疾病的研究热点,大量流行病学及实验证据表明:宫内应激所导致“印迹”效应可“程序化”影响成年后心血管疾病(如高血压等)的发生,并发现RAS在高血压发病过程中起重要作用。然而,妊娠期母鼠脱水是否对成年子代的RAS产生印迹效应,是否影响子代RAS对体液平衡及心血管功能的调控,目前国内外尚未见报道。因此,本实验研究妊娠晚期母鼠脱水对胎鼠RAS和心脏、肾脏发育的影响,并研究脱水对成年子代大鼠RAS的印迹效应及其功能的影响。
第一部分妊娠晚期母鼠脱水对胎儿及其RAS发育的影响
目的:妊娠晚期母鼠脱水对胎儿的调控因素RAS及心脏、肾脏发育的影响。
方法:妊娠晚期母鼠脱水三天后,称量胎鼠体重、心重、肾重及其干重;血气分析仪检测母、胎鼠的血气指标和电解质,用渗透压仪检测血浆渗透压;用放射免疫法检测母、胎鼠血液中血管紧张素(angiotension, Ang)Ⅰ、AngⅡ、血管加压素(vasopressin,VP)和醛固酮(aldosterone,ALD)的浓度;用透射电镜方法检测胎鼠心、肾脏组织超微结构,并用激光多谱勒检测肾脏表面血流;用western blot和荧光定量PCR的方法检测胎鼠心脏、肾脏中血管紧张素受体(ATR)的蛋白和mRNA水平,并检测胎鼠肝脏中血管紧张素原(angiotensinogen, ATG)的mRNA水平。
结果:妊娠晚期母鼠脱水可使胎鼠体重、心脏和肾脏的重量明显降低,胎鼠血钠、红细胞压积及血浆渗透压增加,胎鼠血液中AngI、AngⅡ、VP和ALD的浓度明显增加,及肝脏中ATG的mRNA水平显著增加。妊娠晚期脱水可导致胎鼠心脏及肾脏超微结构的改变,明显增加胎鼠心脏中AT2R的mRNA和蛋白水平,但不影响AT1aR及AT1bR的mRNA和AT1R的蛋白水平;可明显增加胎鼠肾脏中AT1R与AT2R的mRNA和蛋白水平,并减少肾血流量。
结论:妊娠晚期脱水可明显改变胎鼠体内的RAS水平,并影响胎鼠心脏和肾脏的发育。
第二部分妊娠晚期母鼠脱水对成年子代RAS的“印迹”效应及其功能的影响
目的:研究妊娠晚期母鼠脱水对成年子代大鼠体内RAS水平的影响及其“印迹”效应,并研究妊娠晚期母鼠脱水对成年子代大鼠RAS调控体液平衡及心血管系统功能的影响。
方法:用妊娠晚期母鼠脱水组及对照组成年子代,检测子代大鼠体重、心脏和肾脏重量。在基础状态下,用血气分析仪检测成年子代大鼠血气指标和电解质,用渗透压仪检测血浆渗透压;用放射免疫法检测血液中AngI、AngⅡ、VP和ALD的浓度;检测成年子代大鼠心血管系统对PD123319、Losartan及AngII的应答;检测离体胸主动脉及肠系膜动脉对血管舒缩物质的反应;用western blot和荧光定量PCR的方法检测心脏及肾脏中AT1R和AT2R的蛋白和mRNA水平,并检测肝脏中ATG的mRNA水平。在脱水应激下,检测成年子代大鼠体内RAS组分的浓度,并检测脱水对成年子代大鼠体液平衡、心血管系统及饮水饮盐行为的影响。
结果:妊娠晚期母鼠脱水组雌、雄性成年子代大鼠的体重、心脏及肾脏的重量、血气指标及电解质、血液中AngI、AngⅡ、VP和ALD的浓度与对照组比较无差异,但脱水组成年子代大鼠肝脏中ATG mRNA水平及心脏、肾脏中AT1R与AT2R的mRNA和蛋白水平均明显不同于对照组。与对照组比较,脱水组雄性成年子代大鼠对AngⅡ、Losartan及PD123319的反应均明显增强,而雌性子代无差异性,但雌、雄性成年子代大鼠的压力反射敏感性均明显降低。脱水组成年子代大鼠的胸主动脉及肠系膜动脉对AngⅡ的收缩血管反应均明显增强。成年期脱水48h后,脱水组的雌、雄性成年子代鼠血气指标及电解质与对照组比较无差异性,但血浆中AngⅡ、VP和ALD的浓度明显高于对照组,饮盐量和血压也明显升高。
结论:妊娠晚期母鼠脱水对成年子代大鼠的RAS有“印迹”效应。脱水组雌、雄性成年子代大鼠对心血管系统的调控存在性别差异,压力反射敏感性降低可能是子代心血管系统应答“程序化”效应的共同机制。脱水组成年子代大鼠的血管对AngⅡ升高血压的敏感性增强,提示其发生高血压等心血管疾病的危险性明显升高。脱水组成年子代大鼠在脱水刺激时,AngⅡ、ALD及VP浓度升高更明显,这与饮盐量及血压的显著增加可能相关,表现为患高血压等心血管疾病的“易感性”提高。
第三部分妊娠晚期母鼠脱水对雄性成年子代大鼠心脏和肾脏蛋白质组影响的初探
目的:妊娠晚期母鼠脱水对雄性成年子代大鼠心脏和肾脏蛋白质组表达影响。
方法:采用双向电泳技术检测对照组及脱水组雄性成年子代大鼠心脏和肾脏中蛋白质组表达的差异。
结果:雄性成年子代大鼠心脏和肾脏组织中蛋白质分布模式在对照组和实验组之间基本一致。对照组和实验组心脏中获得的平均蛋白质斑点数分别为603±25及577±32个,差异点数为33个;而肾脏中平均蛋白质斑点数分别为975±30及1107±42个,差异点数为38个。
结论:初步建立了分辨率较高、重复性较好的正常和脱水组成年子代大鼠心脏与肾脏中总蛋白质双向电泳图谱。妊娠晚期母鼠脱水影响雄性成年子代大鼠心脏和肾脏中蛋白质组的表达。
Background: Women may face mild to severe dehydration due to exercise, fever, hemorrhage, vomiting, and diarrhea during pregnancy. Water deprivation (WD) is a potent stimulation to affect body fluid balance, and can lead to both extracellular and intracellular dehydration. Renin-angiotensin system (RAS), as an endocrine system, plays a role in regulating body fluid balance, cardiovascular system, neuroendocrine activity, and water and salt intake. A lot of evidence suggests that WD could induce changes in body fluid balance and RAS components in adults. However, it is largely unknown of effects of WD during pregnancy on the development of fetal RAS, and of the heart and kidney.
Barker theory hypothesizes diseases in fetal origins. There is now a body of substantial epidemiological and experimental evidence showing that intrauterine stress may program cardiovascular diseases such as hypertension in late life. Previous studies suggested that the RAS may play a critical role in pathophysiological progress of hypertension induced by adverse environment during fetal development. It is unknown whether exposure to prenatal WD can affect the RAS in its regulation of body fluid balance and cardiovascular system in the offspring. Hence, this project studies the effect of maternal WD during late term on the development of RAS, heart, kidney in both fetuses and offspring.
PART 1 Effects of maternal WD during late gestation on development of fetus and fetal RAS
Objective: To determine the development of the RAS, heart and kidney of the fetus exposure to WD at late term.
Methods: After three days of maternal WD, fetal body, heart, and kidney were weighted, and fetal blood gases and electrolytes were determined with a Nova analyzer, plasma osmolality was determined with an advanced digmatic osmometer. Both fetal and maternal plasma angiotensin (Ang)Ⅰ, AngⅡ, vasopressin (VP) and aldosterone (ALD) concentrations were measured by radioimmunoassay. The ultrastructures of fetal heart and kidney were detected by a transmission electron microscope and the renal blood flow was detected by a Laser Doppler. Protein and mRNA of AngⅡreceptors (ATR) in the fetal heart and kidney were determined with western-blot or real-time PCR, and ATG mRNA in the fetal liver was also determined.
Results: Prenatal exposure to WD at late term significantly decreased weight of the fetal body, heart and kidney, and increased fetal plasma Na+, hematocrit and osmolality. Fetal liver ATG mRNA, plasma AngⅠ, AngⅡ, VP, and ALD concentrations were also increased following WD. Maternal WD during late gestation changed the ultrastructures in the fetal heart and kidney, and altered the expression of both protein and mRNA of ATR in the fetal kidney and heart. Fetal renal blood flow was reduced.
Conclusion: Three days of maternal WD during late gestation significantly changed the concentrations of fetal RAS components, and affected the development of fetal heart and kidney.
PART 2 Imprinting effect and function of RAS of adult offspring exposure to maternal WD during late gestation
Objective: To determine the effect of maternal WD during late gestation on the RAS and its roles in regulation of body fluids and cardiovascular system in offspring. Methods: The offspring in both the control and WD groups were used. The adult offspring body, heart, and kidney were weighted. Blood gases and electrolytes were determined with a Nova analyzer, plasma osmolality was determined with an advanced digmatic osmometer, plasma AngⅠ, AngⅡ, VP, and ALD concentrations were measured by radioimmunoassay. Cardiovascular responses to intravenous injection of PD, losartan, and AngⅡ, and contractility of the thoracic aorta and mesenteric artery were determined. Protein and mRNA of ATR were measured with western blot and real-time PCR in both the heart and kidney of offspring, and ATG mRNA in fetal liver was also determined. The effect of WD on the RAS, body fluid balance, cardiovascular system, and both salt and water intake, offspring was determined.
Results: Maternal WD during late gestation did not change the weights of body, heart and kidney, the blood gases and electrolytes, the concentrations of plasma AngⅠ, AngⅡ, VP and ALD in adult offspring, but maternal WD during late gestation significantly changed the ATG mRNA levels in liver, and both ATR mRNA and proteins in both heart and kidney in adult offspring. Cardiovascular responses to injection of PD, losartan and AngⅡwere notably enhanced in male not female adult offspring in WD group compared to control, but baroreflex sensitivity was notably attenuated in both male and female offspring. Compared to control, the ability of both thoracic aorta and mesenteric artery to vasoconstriction to AngⅡwas enhanced in adult offspring of WD group. After 48h of WD again, blood gases and electrolytes had no difference in adult offsprings between control and WD group, but the concentrations of plasma AngⅡ, VP and ALD, salt intake and blood pressure were significantly elevated in adult offsprings in WD group than those of control.
Conclusion: Maternal WD during late gestation showed chronic influence on the RAS in the offspring. Cardiovascular responses to the stimulation following exposure to prenatal WD showed difference that was gender-dependent. The decrease of baroreflex sensitivity may be the mechanism for changes in the cardiovascular responses. Blood pressure and vasoconstriction to AngⅡwere significantly increased in the adult offspring exposure to prenatal WD. Response to stimulation, plasma AngⅡ, VP, and ALD concentrations were higher in the offspring exposure to prenatal WD than in the control, associated with an increase of salt intake. The data indicate an increase of risks for cardiovascular diseases such as hypertension in the adult offspring exposed to maternal WD during late gestation.
PART 3 Effects of maternal WD during late gestation on expression of proteome in the heart and kidney of the offspring
Objective: To determine the expression of proteome in both the heart and kidney in the adult male offspring exposure to maternal WD during late gestation.
Methods: Two dimensional electrophoresis (2-DE) was used to detect differences of proteome expression between the control and WD group in the heart and kidney of the adult male offspring.
Results: The basic distributions of total proteins were similar in both the heart and kidney in offsprings between the control and WD groups. The numbers of total proteins were 603±25 and 577±32 in the heart between the control and WD groups, in which thirty-three differential protein spots were identified. Total proteins were 975±30 and 1107±42 in the kidney between the control and WD groups, in which thirty-eight differential protein spots were identified.
Conclusion: 2-DE profiles with high resolution and reproducibility of total proteins were established in both the heart and kidney between the control and WD groups, and the expressions of differential proteins were found.
引文
1.中国提高出生人口素质、减少出生缺陷和残疾行动计划(2002-2010):卫生部中国残疾卫基妇发(2002-162号文件).
2. Barker DJ. The fetal origins of diseases of old age. Eur.J.Clin.Nutr. 1992; 46: S3-S9
3. Barker DJ. Intrauterine programming of adult disease. Mol.Med.Today, 1995; 1: 418-423.
4. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ, 1989; 298:564–567.
5. Vehaskari VM, Aviles DH, Manning J. Prenatal programming of adult hypertension in the rat. Kidney Int, 2001; 59:238–245.
6. Alexander BT. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension, 2003; 41:457–462.
7. Barker DJP. Fetal programming of coronary heart disease. Trends in Endocrinology and Metabolism, 2002;13(9):364-368
8. Barker DJP, Godfrey KM, Gluckman PD, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. The Lancet, 1993; 341(8850): 938-941.
9. Gilbert JS, Lang AL, Grant AR, Nijland MJ. Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age. J Physiol, 2005; 565:137–147.
10. Edwards LJ, McMillen IC. Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol, 2001; 533:561–570.
11. Hemmings DG, Williams SJ, Davidge ST. Increased myogenic tone in 7-month-oldadult male but not female offspring from rat dams exposed to hypoxia during pregnancy. Am J Physiol Heart Circ Physiol, 2005; 289:H674–H682.
12. Aagaard-Tillery K, McKnight R, Ke X, Branch DW, Rehan V, Lane R. Fetal origins of disease: In utero nicotine exposure epigenetically alters fetal chromatin structure to differentially regulate transcription of the glucocorticoid receptor. Journal of Reproductive Immunology, 2006; 71(2):168
13. Somm E, Schwitzgebel VM, Aubert ML, Hüppi PS. Prenatal nicotine exposure and the programming of metabolic and cardiovascular disorders. Molecular and Cellular Endocrinology, 2009; doi:10.1016/j.mce.2009.02.026
14. Xiao D, Xu Z, Huang X, Longo LD, Yang S, Zhang L. Prenatal gender-related nicotine exposure increases blood pressure response to angiotensinⅡin adult offspring. Hypertension, 2008; 51:1239-1247.
15. Ji LL, Gottlieb HB, Penny ML, et al: Differential effects of water deprivation and rehydration on Fos and FosB/ΔFosB staining in the rat brainstem. Experimental Neurology, 2007; 203(2): 445-456.
16. Kim YC, Lee I, Kim SG, et al: Effects of glucose supplementation on the pharmacokinetics of intravenous chlorzoxazone in rats with water deprivation for 72 h. Life Sciences, 2006; 79(23): 2179-2186.
17.姚泰,主编.生理学(七年制或八年制),人民卫生出版社. 2005.8第一版
18. McKinley MJ, Denton DA, Ne lson JF, et al. Dehydration induces sodium depletion in rats, rabbits, and sheep. Am J Physiol Regulatory Integrative Comp Physiol, 1983; 45:R287–R292.
19. Chatelain D, Montel V, Dickes-Coopman A, et al. Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat. Regul Pept, 2003,110:249-255.
20. Gottlieb HB, Ji LL, Jones H, et al. Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat. Am J Physiol Regul Integr Comp Physiol, 2006; 290:R1251-261.
21. Salas SP, Giacaman A, Vio CP. Renal and Hormonal Effects of Water Deprivation in Late-Term Pregnant Rats. Hypertension, 2004; 44:334-339.
22. Deloof S, De Seze C, Montel V, et al. Effects of water deprivation on atrial natriuretic peptide secretion and density of binding sites in adrenal glands and kidneys of maternaland fetal rats in late gestation. European Journal of Endocrinology, 1999; 141:160–168.
23. Re RN. Mechanisms of disease: local renin-angiotensin-aldosterone systems and the pathogenesis and treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med, 2004; 1(1):42-7.
24. Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev, 2006; 86(3):747-803.
25. De Gasparo M, Catt KJ, Inagami T, et al. International union of pharmacology. XXⅡI. The angiotensinⅡreceptors. Pharmacol Rev, 2000; 52:415–472.
26. Iwai N, Inagami T.Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Letters, 1992; 298:257-260
27. Rahman M, Kimura S, Nishiyama A, Hitomi H, Zhang G, Abe Y. Angiotensin II stimulates superoxide production via both angiotensin AT1A and AT1B receptors in mouse aorta and heart. Eur J Pharmaco, 2004; 485(1-3):243-9.
28. Schutz S, Le Moullec J.M, Corvol P, Gasc J.M. Early expression of all components of the renin–angiotensin system in human development. Am. J. Pathol, 1996; 149(6): 2067–2079.
29. Robillard JE, Page WV, Mathews MS, Schutte BC, Nuyt AM, Segar JL. Differential gene expression and regulation of renal angiotensinⅡreceptor subtypes (AT1 and AT2) during fetal life in sheep. Pediatr Res, 1995; 38:896–904.
30. Shi L, Yao J, Koos BJ, Xu Z. Induced fetal depressor or pressor responses associated with c-fos by intravenous or intracerebroventricular losartan. Developmental Brain Research, 2004; 153(1):53–60.
31. El-Haddad MA., Ismail Y, Gayle D, and Ross MG. Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus. Am J Physiol Regul Integr Comp Physiol, 2005; 288(4): R1014–R1020.
32. Yamada T, Akishita M, Pollman MJ, Gibbons GH, Dzau VJ, Horiuchi M. Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis and antagonizes angiotensin II type 1 receptor action: An in vitro gene transfer study. Life Sciences, 1998; 69:PL289-PL295.
33. Tanaka M, Ohnishi J, Ozawa Y, Sugimoto M, Usuki S, Naruse M, Murakami K, Miyazaki H. Characterization of angiotensin II receptor type 2 during differentiationand apoptosis of rat ovarian cultured granulosa cells. Biochemical and Biophysical Research Communications, 1995; 207:593-598.
34. Okamura K, Ito M, Chinushi M, Kodama M, Aizawa Y.Angiotensin 2 type 1 receptor blocker attenuates atrial structural remodeling in spontaneously hypertensive rats: Role of the suppression of atrial oxidative stress. Journal of Molecular and Cellular Cardiology, 2006; 41:1053-1054.
35. Voros S, Yang Z, Bove CM, Gilson WD, Epstein FH, French BA, Berr SS, Bishop SP, Conaway MR, Matsubara H, Carey RM, Kramer CM. Interaction between AT1 and AT2 receptors during postinfarction left ventricular remodeling, Am. J. Physiol. Heart Circ. Physiol, 2006; 290:H1004–H1010.
36. Carey RM, Jin XH, Siragy HM. Role of the angiotensin AT2 in blood pressure regulation and therapeutic implications. Am J Hypertens, 2001; 14(6pt 2):98S–102S.
37. Sanvitto GL, J?hren O, Hauser W, Saavedra JM. Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary. Am. J. Physiol, 1997; 273:E156–E163.
38. Barth SW, Gerstberger R. Differential regulation of angiotensinogen and AT1A receptor mRNA within the rat subfornical organ during dehydration. Molecular Brain Research, 1999;64:151-164.
39. Andersson B. The effects of injection of hypertonic NaCl solutions into different parts of the hypothalamus of goats. Acta Physiol Scand, 1953;28:188-201.
40. Fitzsimons JT. The physiological basis of thirst. Kidney Int, 1976;10:3-11.
41. Fitzsimons JT. Angiotensin, thirst and sodium appetite. Physiol Rev, 1998;78:583-686.
42. Epstein AN. Epilogue: Retrospect and prognosis. In: EpsteinAN, Kissileff HR, Stellar E, Eds. The Neuropsychology of Thirst: New Findings and Advances in Concepts. Washington, DC:VHWinston 1973; 315–322.
43. Fitzsimons JT. Some historical perspectives in the physiology of thirst. In: Epstein AN,Kissileff HR, Stellar E, Eds. The Neuropsychology of Thirst: New Findings and Advances in Concepts.Washington, DC: VHWinston, 1973: 3–33.
44. Johnson AK, Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms. Front. Neuroendocrinol,1997;18: 292–353.
45. Wirth JB, Epstein AN. Ontogeny of thirst in the infant rat. Am J Physiol, 1976;230:188-198
46. Xu Z, Ross MG. Appearance of mechanisms for thirst and vasopressin secretion induced by dehydration in near-term rat fetus. Develop Brain Res, 2000;121:11-18.
47. Xu Z, Calvario G, Yao J,.Ross MG, Day L. Central angiotensin induction of fetal brain c-fos expression and swallowing activity. Am J Physiol, 2001;280:R1837-1843.
48. Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BMW. Renin-angiotensin system and cardiovascular risk. Lancet, 2007;369:1208–1219.
49. Jones A, Dhamrait SS, Payne JR, et al. Genetic variants of angiotensin II receptors and cardiovascular risk in hypertension. Hypertension, 2003; 42: 500–506.
50. Jandeleit-Dahm KA, Tikellis C, Reid CM, Johnston CI,Cooper ME. Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens, 2005; 23:463–473.
51. Mao C, Wu J, Xiao D, Lv J, Ding Y, Xu Z, Zhang L. The effect of fetal and neonatal nicotine exposure on renal development of AT1 and AT2 receptors. Reprod Toxicol (2009), doi:10.1016/j.reprotox.2009.01.012.
52. Mao C, Zhang H, Xiao D, Zhu L, Ding Y, Zhang Y, Wu L, Xu Z, Zhang L.Perinatal nicotine exposure alters AT1 and AT2 receptor expression pattern in the brain of fetal and offspring rats. Brain Research, 2008; 1243:47-52.
53. Bogdarina I, Welham S, King PJ, Burns SP, Clark AJL. Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res, 2007; 100:520-526.
1. McKinley MJ, Denton DA, Ne lson JF, et al. Dehydration induces sodium depletion in rats, rabbits, and sheep. Am J Physiol Regulatory Integrative Comp Physiol, 1983; 45:R287–R292.
2. Re RN. Mechanisms of disease: local renin-angiotensin-aldosterone systems and the pathogenesis and treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med, 2004; 1(1):42-7.
3. Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev, 2006; 86(3):747-803.
4. Gottlieb HB, Ji LL, Jones H, et al. Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat. Am J Physiol Regul Integr Comp Physiol, 2006; 290:R1251-261.
5. Chatelain D, Montel V, Dickes-Coopman A, et al. Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat. Regul Pept, 2003; 110:249-255.
6. Salas SP, Giacaman A, Vio CP. Renal and Hormonal Effects of Water Deprivation in Late-Term Pregnant Rats. Hypertension, 2004; 44:334-339.
7. Deloof S, De Seze C, Montel V, et al. Effects of water deprivation on atrial natriuretic peptide secretion and density of binding sites in adrenal glands and kidneys of maternal and fetal rats in late gestation. European Journal of Endocrinology, 1999; 141:160–168.
8. Mao C, Guan J, Yuan X, et al. Got pure blood in fetal rats? Pediatric hematology and oncology, 2007; 24:457-460.
9. De Luca LA Jr., Xu Z, Schoorlemmer GHM, Thunhorst RL, Beltz TG, Menani JV,et al. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes. Am J Physiol Regulatory Integrative Comp Physiol, 2002; 282:R552–R559.
10. Makino Y, Minamino N, Kakishita E, Kangawa K, Matsuo H. Natriuretic peptides in water-deprived and in salt-loaded rats. Peptides, 1996;17:1031–1039.
11. Di Nicolantonio R, Mendelsohn FAO. Plasma renin and angiotensin in dehydrated and rehydrated rats. Am J Physiol, 1986; 250:R898–R901.
12. Israel A, Saavedra JM, Plunkett L. Water deprivation upregulates angiotensinⅡreceptors in rat anterior pituitary. Am J Physiol, 1985; 248:E264-267.
13. De Gasparo M, Catt KJ, Inagami T, et al. International union of pharmacology. XXⅡI. The angiotensinⅡreceptors. Pharmacol Rev, 2000; 52:415–472.
14. Johren O, Inagami T, Saavedra JM. AT1A, AT1B, and AT2 angiotensin II receptor subtype gene expression in rat brain. Neuroreport, 1995; 6(18):2549-52.
15. Rahman M, Kimura S, Nishiyama A, Hitomi H, Zhang G, Abe Y. Angiotensin II stimulates superoxide production via both angiotensin AT1A and AT1B receptors in mouse aorta and heart. Eur J Pharmacol, 2004; 485(1-3):243-9.
16. Schutz S, Le Moullec JM, Corvol P, Gasc JM. Early expression of all components of the renin–angiotensin system in human development. Am J Pathol, 1996; 149(6): 2067–2079.
17. Robillard JE, Page WV, Mathews MS, Schutte BC, Nuyt AM, Segar JL. Differential gene expression and regulation of renal angiotensinⅡreceptor subtypes (AT1 and AT2) during fetal life in sheep. Pediatr Res, 1995; 38:896–904.
18. Maric C, Aldred GP, Harris PJ, Alcorn D. Angiotensin II inhibits growth of cultured embryonic renomedullary interstitial cells through the AT2 receptor. Kidney Int, 1998; 53(1):92-9.
19. Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci U S A, 1995; 92(23):10663-7.
20. Shanmugam S, Llorens-Cortes C, Clauser E, Corvol P, Gasc JM. Expression of angiotensin II AT2 receptor mRNA during development of rat kidney and adrenal gland. Am J Physiol, 1995; 268(5 Pt 2):F922-30.
21. Norwood VF, Craig MR, Harris JM, Gomez RA. Differential expression of angiotensin II receptors during early renal morphogenesis. Am J Physiol, 1997; 272(2 Pt 2):R662-8.
22. Guron G, Friberg P. An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertens, 2000; 18(2):123-37.
23. Chen Y, Lasaitiene D, Friberg P. The renin-angiotensin system in kidney development. Acta Physiol Scand, 2004; 181(4):529-35.
1. Barker DJ. The fetal origins of diseases of old age. Eur.J.Clin.Nutr. 1992; 46: S3-S9
2. Barker DJ. Intrauterine programming of adult disease. Mol.Med.Today. 1995; 1: 418-423.
3. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989; 298:564–567.
4. Edwards LJ, McMillen IC. Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol 2001; 533:561–570.
5. Gilbert JS, Lang AL, Grant AR, Nijland MJ. Maternal nutrient restriction in heep: hypertension and decreased nephron number in offspring at 9 months of age. J Physiol 2005; 565:137–147.
6. Vehaskari VM, Aviles DH, Manning J. Prenatal programming of adult hypertension in the rat. Kidney Int 2001; 59:238–245.
7. Hemmings DG, Williams SJ, Davidge ST. Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy. Am J Physiol Heart Circ Physiol 2005; 289:H674–H682.
8. Alexander BT. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension 2003; 41:457–462.
9. Ortiz LA, Quan A, Zarzar F, Weinberg A, Baum M. Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension 2003; 41:328–334.
10. Franco Mdo C, Akamine EH, Di Marco GS, Casarini DE, Fortes ZB, Tostes RC, et al. NADPH oxidase and enhanced superoxide generation in intrauterine undernourished rats: involvement of the renin-angiotensin system. Cardiovasc Res 2003; 59:767–775.
11. Hadoke PW, Lindsay RS, Seckl JR, Walker BR, Kenyon CJ. Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure. J Endocrinol 2006; 188:435– 442.
12. Langley-Evans SC, Sherman RC, Welham SJ, Nwagwu MO, Gardner DS, Jackson AA. Intrauterine programming of hypertension: the role of the renin-angiotensin system. Biochem Soc Trans 1999; 27:88–93.
13. Xiao D, Xu Z, Huang X, Longo LD, Yang S, Zhang L. Prenatal gender-related nicotine exposure increases blood pressure response to angiotensinⅡin adult offspring. Hypertension 2008; 51:1239-1247.
14. Bol VV, Reusens BM, Remacle CA. of rat preadipocytes. Obesity (Silver Spring). 2008;16(12):2760-3.
15. Torre P, Ladaki C, ScirèG, Spadoni GL, Cianfarani S. Catch-up growth in body mass index is associated neither with reduced insulin sensitivity nor with altered lipid profile in children born small for gestational age. J Endocrinol Invest. 2008;31(9):760-4.
16. Dulloo AG. Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance. Best Pract Res Clin Endocrinol Metab. 2008 Feb;22(1):155-71.
17. Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D, The fetal and childhood growth of persons who develop type II diabetes. Ann. Intern. Med. 2000;133, 176–182.
18. Barker DJ, Osmond C, Forsen TJ et al. Trajectories of growth among children who have coronary events as adults. The New England Journal of Medicine. 2005; 353: 1802–1809.
19. Huxley RR, Shiell AW& Law CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature.Journal of Hypertension. 2000; 18: 815–831.
20. Li G, Bae S, Zhang L. Effect of prenatal hypoxia on heat stress-mediated cardioprotection in adult rat heart. Am J Physiol Heart Circ Physiol 2004; 286:H1712–H1719.
21. Dodic M, Samuel C, Moritz K, Wintour EM, Morgan J, Grigg L, Wong J. Impaired cardiac functional reserve and left ventricular hypertrophy in adult sheep after prenatal dexamethasone exposure. Circ Res 2001; 89:623–629.
22. Segar JL, Roghhair RD, Segar EM, Bailey MC, Scholz TD, Lamb FS. Early gestation dexamethasone alters baroreflex and vascular responses in newborn lambs before hypertension. Am J Physiol Regul Integr Comp Physiol 2006; 291:R481–R488.
23. Pechère-Bertschi A, Burnier M. Female sex hormones, salt, and blood pressure regulation.American Journal of Hypertension,2004,17(10): 994-1001.
24. Weinberg EO, Thienelt CD, Katz SE, Bartunek J, Tajima M, Rohrbach S, Douglas PS, Lorell BH. Gender differences in molecular remodeling in pressure overload hypertrophy. Journal of the American College of Cardiology, 1999, 34(1):264-273.
25. Douglas PS, Katz SE, Weinberg EO, Chen MH, Bishop SP, Lorell BH. Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload. Journal of the American College of Cardiology, 1998,32(4):1118-1125
26. Lu F, Bytautiene E, Tamayo E, Gamble P, Anderson GD, Hankins GDV, Longo M, Saade GR. Gender-specific effect of overexpression of sFlt-1 in pregnant mice on fetal programming of blood pressure in the offspring later in life. American Journal of Obstetrics and Gynecology, 2007,197(4):418.e1-418.e5.
27. Almeida JR, Mandarim-de-Lacerda CA. Overweight is gender-dependent in prenatal protein–calorie restricted adult rats acting on the blood pressure and the adverse cardiac remodeling. Life Sciences, 2005; 77(2):1307-1318.
28. Touyz RM, Endeman D, He G, Li JS, Schiffrin EL. Role of AT2 receptors in angiotensin II-stimulated contraction of small mesenteric arteries in young SHR. Hypertension. 1999;33:366–372.
29. Scheuer DA, Perrone MH. Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin. Am J Physiol. 1993;264:R917–R923.
30. Chatziantoniou C, Arendshorst WJ. Angiotensin receptor sites in renal vasculature of rats developing genetic hypertension. Am J Physiol. 1993;265:F853–F862.
31. Salas SP, Giacaman A, Vio CP. Renal and Hormonal Effects of Water Deprivation in Late-Term Pregnant Rats[J]. Hypertension, 2004,44:334-339.
32. De Luca LA Jr., Xu Z, Schoorlemmer GHM, Thunhorst RL, Beltz TG, Menani JV, et al. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes. Am J Physiol Regulatory Integrative Comp Physiol 2002; 282:R552–R559.
33. Makino Y, Minamino N, Kakishita E, Kangawa K, Matsuo H. Natriuretic peptides in water-deprived and in salt-loaded rats. Peptides 1996;17:1031–1039.
34. Gharbi N, Somody L, El Fazaa S, Kamoun A, Gauquelin-Koch G, Gharib C. Tissue norepinephrine turnover and cardiovascular responses during intermittent dehydration in the rat. Life Sciences.1999, 64(25):2401-2410.
35. Gardiner SM. Bennett T. Interactions between neural mechanisms, the renin-angiotensin system and vasopressin in the maintenance of blood pressure during water deprivation: studies in Long Evans and Brattleboro rats. Clinical Science. 1985, 68(6):647-57.
36. Gottlieb HB, Ji LL, Jones H, et al. Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat[J]. Am J Physiol Regul Integr Comp Physiol, 2006,290:R1251-261.
37. Chatelain D, Montel V, Dickes-Coopman A, et al. Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat[J]. Regul Pept, 2003,110:249-255.
38. Israel A, Saavedra JM, Plunkett L. Water deprivation upregulates angiotensinⅡreceptors in rat anterior pituitary. Am J Physiol 1985; 248:E264-267.
39. Re RN. Mechanisms of disease: local renin-angiotensin-aldosterone systems and the pathogenesis and treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2004;1(1):42-7.
40. Rockhold RW. Share L. Crofton JT. Brooks DP. Cardiovascular response to vasopressin vasopressor antagonist administration during water deprivation in the rat. Neuroendocrinology. 1984,38(2):139-44.
41. Gregory LC. Quillen EW Jr. Keil LC. Chang D. Reid IA. Effect of vasopressin blockade on blood pressure during water deprivation in intact and baroreceptor-denervated conscious dogs. American Journal of Physiology.254(4):E490-5, 1988
42. Di Nicolantonio R, Mendelsohn FAO. Plasma renin and angiotensin in dehydrated and rehydrated rats. Am J Physiol 1986; 250:R898–R901.
43. Brooks VL. Keil LC. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation. American Journal of Physiology. 1992,263(4):R762-9.
44. Ramsay DJ, Thrasher TN, and Bie P. Endocrine components of body fluid homeostasis. Comp Biochem Physiol A. 1988,90:777–780.
45. Rowland NE and Fregly MJ. Repletion of acute sodium deficit in rats drinking either low or high concentrations of sodium chloride solution. Am J Physiol Regulatory Integrative Comp Physiol.1992, 262: R419–R425.
46. McKinley MJ, Denton DA, Ne lson JF, et al. Dehydration induces sodium depletion in rats, rabbits, and sheep[J]. Am J Physiol Regulatory Integrative Comp Physiol, 1983,45:R287–R292.
47. Epstein AN. Epilogue: Retrospect and prognosis. In: EpsteinAN, Kissileff HR, Stellar E, Eds.The Neuropsychology of Thirst: New Findings and Advances in Concepts. Washington, DC:VHWinston 1973; 315–322.
48. Fitzsimons JT. Some historical perspectives in the physiology of thirst. In: Epstein AN,Kissileff HR, Stellar E, Eds. The Neuropsychology of Thirst: New Findings and Advances in Concepts.Washington, DC: VHWinston, 1973: 3–33.
49. De Luca LA Jr. Vendramini RC. Pereira DT. Colombari DA. David RB. de Paula PM. Menani JV. Water deprivation and the double- depletion hypothesis: common neural mechanisms underlie thirst and salt appetite. Brazilian Journal of Medical & Biological Research. 2007;40(5):707-12.
50. De Wardener HE and MacGregor GA. Sodium and blood pressure. Curr Opin Cardiol. 2002; 17(4): 360-367.
51. Contreras,R.J. High NaCl intake of rat dams alters maternal behavior and elevates blood pressure of adult offspring. Am J Physiol 1993;264:R296-304.
52. Xu Z, Shi L, Yao J. Central angiotensin II induced pressor responses and neural activity in utero and hypothalamic angiotensin receptors in pre-term ovine fetus. Am. J. Physiol (Heart & Circulation). 2004, 286: H1507-1514.
53. Fitzsimons JT. Angiotensin, thirst and sodium appetite. Physiol Rev 1998;78:583-686
54. Johnson AK, Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms. Front. Neuroendocrinol.18: 292–353, 1997.
55. Malvin RL, Mouw D, Vander AJ. Angiotensin: physiological role in water-deprivation-induced thirst of rats. Science. 1977,197(4299):171-3.
56. Sato MA. Yada MM. De Luca LA Jr. Antagonism of the renin-angiotensin system and water deprivation-induced NaCl intake in rats. Physiology & Behavior. 1996, 60(4):1099-104
57. Barney CC, Threatte RM, Fregly MJ. Water deprivation-induced drinking in rats: role of angiotensin II. Am J Physiol.1983,244(2):R244-8.
1. Bollag DM, Edelstein SS. Protein Methods. 2nd. New York: Wiley-Liss, Inc. 1996, 50-55.
2. Wasinger VC. Progress with gene-product mapping of the mollicutes: Mycoplasma genitalium. Electrophoresis, 1995; 16(7) : 1090-1094.
3. Kahn P. From genome to proteome: looking at a cell’s proteins. Science, 1995;270 (5235) : 369-370.
4. Swinbanks D. Government backs proteome proposal. Nature, 1995; 14: 378 (6558): 653.
5. Hochstrasser DF. Proteome in perspective. Clin Chem Lab Med, 1998; 36(11): 825-836
6. Humphery SI, Cordwell SJ, Blackstock WP. Proteome research : complementarity and limitations with respect to the RNA and DNA worlds. Electrophoresis, 1997; 18(8): 1217-1242.
7. Anderson NL, Anderson NG. Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis, 1998; 19 (11): 1853-1861.
8. Bohring C, Krause E, Habermann B, et al. Isolation and identification of sperm membrane antigens recognized by antisperm antibodies, and their possible role in immunological infertility disease. Mol Hum Reprod, 2001; 7(2): 113-118.
9. Lian Z, Wang L, Yamaga S, et al. Genomic and proteomic analysis of the myeloid differentiation program. Blood, 2001; 98(3):513-524.
10. Rattan SI, Derventzi A, Clark BF. Protein synthesis, posttranslational modifications, and aging. Ann N Y Acad Sci, 1992; 663(1):48-62
11. Rattan SI. Synthesis, modifications, and turnover of proteins during aging. Exp Gerontol, 1996; 31(1-2):33-47.
12. Gillery P, Monboisse JC, Maquart FX, et al. Aging mechanisms of proteins. Diabete Metab, 1991; 17(1):1-16.
13. Rosenberger RF. Senescence and the accumulation of abnormal proteins. Mutat Res, 1991; 256 (2-6): 255-262.
14. Lanne B, Potthast F, Hoglund A, Brockenhuus von Low enhielm H, Nystrom AC, N ilsson F, Dahllof B. Thiourea enhances mapping of the proteome from murine white adipose tissue. Proteomics, 2001; 1 (7):819- 828.
15. Rabilloud T, Adessi C, Giraudel A, Lunardi J. Improvement of the solubilization of proteins in two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis, 1997; 18(324):307-316.
[1] Fitzsimons JT. Angiotensin, Thirst, and Sodium Appetite. Physiology review, 78(3):583-686, 1998.
[2] Johnson AK, and Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms of central integration. Frontiers in Neuroendocrinology, 18(3): 292-353, 1997.
[3] Barker DJ, Bagby SP. Developmental antecedents of cardiovascular disease: a historical perspective. J Am Soc Nephrol, 16(9):2537-2544, 2005.
[4] Yzydorczyk C, Gobeil F, Cambonie G, Lahaie I, Le NL, Samarani S, Lavoie JC, Oligny L, Pladys P, Hardy P, Nuyt AM. Exaggerated vasomotor response to angiotensinⅡin rats with fetal programming of hypertension associated with exposure to a low protein diet during gestation. Am J Physiol Regul Integr Comp Physiol, 291(4):R1060-R1068, 2006.
[5] Schutz S, Le Moullec J.M, Corvol P, Gasc J.M. Early expression of all components of the renin–angiotensin system in human development. Am. J. Pathol, 149(6): 2067–2079, 1996.
[6] Butkus A, Albiston A, Alcorn D, Giles M, McCausland J, Moritz K, Zhuo J, WintourEM. Ontogeny of angiotensin II receptors, types 1 and 2, in ovine mesonephros and metanephros. Kidney Int, 52(3):628–636, 1997.
[7] Wintour EM, Alcom D, Rockell MD. Development and function of the fetal kidney. In Brace RA, ed. Fetus and Neonate, Volume IV.1997.
[8] Rawashdeh NM, Rose JC, Rogers MS, Giammattei C, Iskandar SS. Immunocytochemical localization of renin in the developing ovine fetus. Reprod Fertil Dev, 8(1):97-101, 1996.
[9] Wang J, Perez FM, and Rose JC. Developmental Changes in Renin-Containing Cells From the Ovine Fetal Kidney. J Soc Gynecol Invest, 4(4): 191-196, 1997.
[10] Moritz K, Koukoulas I, Albiston A, Wintour EM. Angiotensin II infusion to the midgestation ovine fetus: effects on the fetal kidney. Am J Physiol, 279(4 pt 2):R1290–R1297, 2000.
[11] Xu Z, Shi L, Hu F, White R, Stewart L, Yao J, In utero development of central ANG-stimulated pressor response and hypothalamic fos expression. Brain Res, 145(2):169– 176, 2003
[12] Stanley JR, Giammattei CE, Sheikh AU, Green JL, Zehnder T and Rose JC. Effects of chronic infusion of angiotensin II on renin and blood pressure in the late-gestation fetal sheep. American Journal of Obstetrics and Gynecology, 176(4): 931-937, 1997.
[13] Chen K, Carey LC, Valego NK, Liu J, Rose JC. Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep. Am J Physiol Regul Integr Comp Physiol, 289(4):R1006–14, 2005.
[14] Tower C, Baker P. The Genetics of fetal growth restriction: Implications for management. Reviews in Gynaecological and Perinatal Practice, 6 (1-2):99–105, 2006.
[15] Zhang XQ, Varner M, Dizon-Townson D, Song F, Ward K. A molecular variant of angiotensinogen is associated with idiopathic intrauterine growth restriction. Obstet Gynecol, 101(2):237–42, 2003.
[16] Robillard JE, Page WV, Mathews MS, Schutte BC, Nuyt AM, Segar JL. Differential gene expression and regulation of renal angiotensin II receptor subtypes (AT1 and AT2) during fetal life in sheep. Pediatr Res, 38(6):896–904, 1995.
[17] Hu F, Morrissey P, Yao J, Xu Z. Development of AT1 and AT2 receptors in the ovine fetal brain. Developmental Brain Research, 150(1):51– 61, 2004.
[18] Shi L, Yao J, Koos BJ, Xu Z. Induced fetal depressor or pressor responses associated with c-fos by intravenous or intracerebroventricular losartan. Developmental Brain Research, 153(1):53–60, 2004.
[19] El-Haddad MA., Ismail Y, Gayle D, and Ross MG. Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus. Am J Physiol Regul Integr Comp Physiol, 288(4): R1014–R1020, 2005.
[20] Carey RM, Jin XH, Siragy HM. Role of the angiotensin AT2 in blood pressure regulation and therapeutic implications. Am J Hypertens, 14(6 pt 2):98S–102S, 2001.
[21] Wood CE. The function of the fetal pituitary-adrenal system. In:Thorburn GD, Harding R, eds. Oxford: Oxford University Press, :351–8,1994.
[22] Challis JR, Brooks AN. Maturation and activation of hypothalamic-pituitary-adrenal function in fetal sheep. Endocr Rev, 10(2):182–204, 1989.
[23] Moritz KM, Boon WC, Wintour EM. Aldosterone secretion by the mid-gestation ovine fetus: role of the AT2 receptor. Molecular and Cellular Endocrinology. ,157(1-2): 153–160, 1999.
[24] Mann SE, Nijland MJ, and Ross MG. Fetal Absorption of Intra-Amniotic Aldosterone: Effects on Urine Composition. J Soc Gynecol Invest, 6(5):252–7, 1999.
[25] Benson CA, Wintour EM. The effect of bilateral adrenalectomy on fluid balance in the ovine fetus. J. Physiol, 489(pt 1):235–241, 1995.
[26] Cameron VA, Aitken GD, Ellmers LJ, Kennedy MA, Espiner EA. The sites of gene expression of atrial, brain, and c-type natriuretic peptide in mouse fetal development: temporal changes in embryos and placenta. Endocrinology, 137(3):817–824, 1996.
[27] Takahashi T, Allen PD, Izumo S. Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Circ Res, 71(1):9–17, 1992.
[28] Johnson DD, Tetzke TA, Cheung CY. Gene expression of atrial natriuretic factor in ovine fetal heart during development. J Soc Gynecol Invest, 1(1):14–18, 1994.
[29] Walther T. Schultheiss HP. Tschope C. Stepan H. Natriuretic peptide system in fetal heart and circulation. J Hypertens, 20(5):785–791, 2002.
[30] Cheung CY. Regulation of atrial natriuretic factor secretion and expression in the ovine fetus. Neurosci Behav Rev, 19(2):159–164, 1995.
[31] Walther T, Stepan H, Faber R. Dual natriuretic peptide response to volume load in fetal circulation. Cardiovasc Res, 49(4):817-819, 2001.
[32] Cameron VA and Ellmers LJ. Minireview: Natriuretic Peptides during Development of the Fetal Heart and Circulation. Endocrinology, 144(6):2191–2194, 2003.
[33] Lim AT, Gude NM. Atrial natriuretic factor production by the human placenta. J Clin Endocrinol Metab, 80(10):3091–3093, 1996.
[34] Dodd A, Kullama LK, Ervin MG, Leake RD, Ross MG. Ontogeny of fetal renal atrium natriuretic factor receptors. Life Sci, 54(15):1101-1107, 1994.
[35] Perreault T, Baribeau J, Gutkowska J. ANF system in the newborn piglet pulmonary vessels. J Cardiovasc Pharmacol, 29(6):740-746, 1997.
[36] Xu H. Hu XY. Wu L. Zhou JN. Neurotensin expressing neurons developed earlier than vasoactive intestinal polypeptide and vasopressin expressing neurons in the human suprachiasmatic nucleus. Neuroscience Letters, 335 (3):175–178, 2003.
[37] Lipari EF, Lipari D, Gerbino A, Di Liberto D, Bellafiore M, Catalano M, Valentino B. The hypothalamic magnocellular neurosecretory system in developing rats. Eur J Histochem, 45(2):163–168, 2001.
[38] Hansenne I. Rasier G. Pequeux C. Brilot F. Renard Ch. Breton C. Greimers R. Legros JJ. Geenen V. Martens HJ. Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network.. Journal of Neuroimmunology, 158(1-2):67– 75, 2005.
[39] Martinez A, Farr A, Vos MD, Cuttitta F, Treston AM. Peptide-amidating enzymes are expressed in the stellate epithelial cells of the thymic medulla. J. Histochem. Cytochem, 46(5):661– 668, 1998.
[40] Arnauld E, Wattiaux JP, Arsaut J, Rostene W, Vincent JD. Alterations in vasopressin and oxytocin messenger RNA in the rat supraoptic nucleus during dehydration-rehydration evaluated by in situ hybridization and northern blotting. Neurosci Lett, 149(2):177-181, 1993.
[41] Ramirez BA. Wang S. Kallichanda N. Ross MG. Chronic in utero plasma hyperosmolality alters hypothalamic arginine vasopressin synthesis and pituitary arginine vasopressin content in newborn lambs. American Journal of Obstetrics and Gynecology, 187(1):191-196, 2002.
[42] Laszlo FA, Laszlo F Jr, De Wied D. Pharmacology and clinical perspectives of vasopressin antagonists. Pharmacol Rev, 43(1):73–108, 1991.
[43] McCann SM, Antunes-Rodrigues J, Jankowski M, Gutkowska J. Oxytocin,vasopressin and atrial natriuretic peptide control body fluid homeostasis by action on their receptors in brain, cardiovascular system and kidney. Prog Brain Res, 139:309–328, 2002.
[44] Nielsen S, Chou CL, Marples D Christensen EI, Kishore BK, Knepper MA. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci USA, 92(4):1013–1017, 1995.
[45] Albuquerque CA. Nijland MJ. Ross MG. Mechanism of arginine vasopressin suppression of ovine fetal lung fluid secretion: lack of V2-receptor effect. Journal of Maternal-Fetal Medicine, 7(4):177-82, 1998.
[46] Varlinskaya EI, Petrov ES, Robinson SR, Smotherman WP. Behavioral effects of centrally administered arginine vasopressin in the rat fetus. Behavioral Neuroscience, 108(2):395-409, 1994.
[47] Xu Z, Hu F, Shi L, Morrissey P, Stewart L, Yao J. Central angiotensin-mediated vasopressin release and activation of hypothalamic neurons in younger fetus at pre-term. Peptides, 26(2):307–314, 2005.
[48] Jensen E, Wood CE, and Keller-Wood M. Alterations in Maternal Corticosteroid Levels Influence Fetal Urine and Lung Liquid Production. J Soc Gynecol Investig, 10(8):480–9, 2003.
[49] Tena JJ, Neto A, de la Calle-Mustienes E, Bras-Pereira C, Casares F, Gomez-Skarmeta JL. Odd-skipped genes encode repressors that control kidney development. Developmental Biology, 301(2):518–531, 2007.
[50] Schedl A and Hastie ND. Cross-talk in kidney development. Current Opinion in Genetics & Development, 10(5):543–549, 2000.
[51] Woolf AS, Price KL, Scambler PJ, Winyard PJ. Evolving concepts in human renal dysplasia. J Am Soc Nephrol, 15(4):998–1007, 2004.
[52] Guignard JP. Renal morphogenesis and development of renal function. In: Taeusch HW, Ballard RA, Gleason CA, editors. Avery’s diseases of the newborn. Philadelphia: Elsevier Saunders; 1258–1259, 2005.
[53] Beck JC, Lipkowitz MS, Abramson RG. Characterization of the fetal glucose transporter in rabbit kidney: comparison with the adult brush border electrogenic Na+-glucose symporter. J Clin Invest, 82(2):379–387, 1988.
[54] Igarashi P, Vanden Heuvel GB, Payne JA, and Forbush B 3rd. Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. Am J Physiol Renal Fluid Electrolyte Physiol, 269(3 pt 2):F405–F418, 1995.
[55] Quigley R, Mulder J, Baum M. Ontogeny of water transport in the rabbit proximal tubule. Pediatric Nephrology, 18(11):1089-1094, 2003.
[56] Bonilla-Felix M and Jiang W. Aquaporin-2 in the immature rat: expression, regulation and trafficking. J Am Soc Nephrol, 8(10): 1502–1509, 1997.
[57] Lumbers ER. Functions of the renin angiotensin system during development. Clin Exp Pharmacol Physiol, 22(8):499-505, 1995.
[58] Bonilla-Felix M. Development of water transport in the collecting duct. Am J Physiol Renal Physiol, 287(6): F1093–F1101, 2004.
[59] Ross MG, Kullama LK, Ogundipe OA, Chan K, Ervin MG. Ovine fetal swallowing response to intracerebroventricular hypertonic saline. J Appl Physiol, 78(6):2267–2271, 1995.
[60] El-Haddad MA, Chao CR, Sayed AA, Ross MG. Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity. Am J Obstet Gynecol,185(4):828–833, 2001.
[61] El-Haddad MA, Chao CR and Ross MG. N-Methyl-D-Aspartate Glutamate Receptor Mediates Spontaneous and Angiotensin II–Stimulated Ovine Fetal Swallowing. J Soc Gynecol Investig, 12(7):504–509, 2005.
[62] Xu Z, Nijland MJ, Ross MG. Plasma osmolality dipsogenic thresholds and c-fos expression in the near-term ovine fetus. Pediatr Res, 49(5):678–685, 2001.
[63] El-Haddad MA, Desai M, Gayle D, and Ross MG. In Utero Development of Fetal Thirst and Appetite: Potential for Programming. J Soc Gynecol Investig, 11(3):123–130, 2004.
[64] Xu Z, Glenda C, Day L. Yao J, Ross MG. Central angiotensin induction of fetal brain c-fos expression and swallowing activity. Am J Physiol Regul Integr Com, 280(6), 2005.
2. Barker DJ. The fetal origins of diseases of old age. Eur.J.Clin.Nutr. 1992; 46: S3-S9
3. Barker DJ. Intrauterine programming of adult disease. Mol.Med.Today, 1995; 1: 418-423.
4. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ, 1989; 298:564–567.
5. Vehaskari VM, Aviles DH, Manning J. Prenatal programming of adult hypertension in the rat. Kidney Int, 2001; 59:238–245.
6. Alexander BT. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension, 2003; 41:457–462.
7. Barker DJP. Fetal programming of coronary heart disease. Trends in Endocrinology and Metabolism, 2002;13(9):364-368
8. Barker DJP, Godfrey KM, Gluckman PD, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. The Lancet, 1993; 341(8850): 938-941.
9. Gilbert JS, Lang AL, Grant AR, Nijland MJ. Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age. J Physiol, 2005; 565:137–147.
10. Edwards LJ, McMillen IC. Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol, 2001; 533:561–570.
11. Hemmings DG, Williams SJ, Davidge ST. Increased myogenic tone in 7-month-oldadult male but not female offspring from rat dams exposed to hypoxia during pregnancy. Am J Physiol Heart Circ Physiol, 2005; 289:H674–H682.
12. Aagaard-Tillery K, McKnight R, Ke X, Branch DW, Rehan V, Lane R. Fetal origins of disease: In utero nicotine exposure epigenetically alters fetal chromatin structure to differentially regulate transcription of the glucocorticoid receptor. Journal of Reproductive Immunology, 2006; 71(2):168
13. Somm E, Schwitzgebel VM, Aubert ML, Hüppi PS. Prenatal nicotine exposure and the programming of metabolic and cardiovascular disorders. Molecular and Cellular Endocrinology, 2009; doi:10.1016/j.mce.2009.02.026
14. Xiao D, Xu Z, Huang X, Longo LD, Yang S, Zhang L. Prenatal gender-related nicotine exposure increases blood pressure response to angiotensinⅡin adult offspring. Hypertension, 2008; 51:1239-1247.
15. Ji LL, Gottlieb HB, Penny ML, et al: Differential effects of water deprivation and rehydration on Fos and FosB/ΔFosB staining in the rat brainstem. Experimental Neurology, 2007; 203(2): 445-456.
16. Kim YC, Lee I, Kim SG, et al: Effects of glucose supplementation on the pharmacokinetics of intravenous chlorzoxazone in rats with water deprivation for 72 h. Life Sciences, 2006; 79(23): 2179-2186.
17.姚泰,主编.生理学(七年制或八年制),人民卫生出版社. 2005.8第一版
18. McKinley MJ, Denton DA, Ne lson JF, et al. Dehydration induces sodium depletion in rats, rabbits, and sheep. Am J Physiol Regulatory Integrative Comp Physiol, 1983; 45:R287–R292.
19. Chatelain D, Montel V, Dickes-Coopman A, et al. Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat. Regul Pept, 2003,110:249-255.
20. Gottlieb HB, Ji LL, Jones H, et al. Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat. Am J Physiol Regul Integr Comp Physiol, 2006; 290:R1251-261.
21. Salas SP, Giacaman A, Vio CP. Renal and Hormonal Effects of Water Deprivation in Late-Term Pregnant Rats. Hypertension, 2004; 44:334-339.
22. Deloof S, De Seze C, Montel V, et al. Effects of water deprivation on atrial natriuretic peptide secretion and density of binding sites in adrenal glands and kidneys of maternaland fetal rats in late gestation. European Journal of Endocrinology, 1999; 141:160–168.
23. Re RN. Mechanisms of disease: local renin-angiotensin-aldosterone systems and the pathogenesis and treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med, 2004; 1(1):42-7.
24. Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev, 2006; 86(3):747-803.
25. De Gasparo M, Catt KJ, Inagami T, et al. International union of pharmacology. XXⅡI. The angiotensinⅡreceptors. Pharmacol Rev, 2000; 52:415–472.
26. Iwai N, Inagami T.Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Letters, 1992; 298:257-260
27. Rahman M, Kimura S, Nishiyama A, Hitomi H, Zhang G, Abe Y. Angiotensin II stimulates superoxide production via both angiotensin AT1A and AT1B receptors in mouse aorta and heart. Eur J Pharmaco, 2004; 485(1-3):243-9.
28. Schutz S, Le Moullec J.M, Corvol P, Gasc J.M. Early expression of all components of the renin–angiotensin system in human development. Am. J. Pathol, 1996; 149(6): 2067–2079.
29. Robillard JE, Page WV, Mathews MS, Schutte BC, Nuyt AM, Segar JL. Differential gene expression and regulation of renal angiotensinⅡreceptor subtypes (AT1 and AT2) during fetal life in sheep. Pediatr Res, 1995; 38:896–904.
30. Shi L, Yao J, Koos BJ, Xu Z. Induced fetal depressor or pressor responses associated with c-fos by intravenous or intracerebroventricular losartan. Developmental Brain Research, 2004; 153(1):53–60.
31. El-Haddad MA., Ismail Y, Gayle D, and Ross MG. Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus. Am J Physiol Regul Integr Comp Physiol, 2005; 288(4): R1014–R1020.
32. Yamada T, Akishita M, Pollman MJ, Gibbons GH, Dzau VJ, Horiuchi M. Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis and antagonizes angiotensin II type 1 receptor action: An in vitro gene transfer study. Life Sciences, 1998; 69:PL289-PL295.
33. Tanaka M, Ohnishi J, Ozawa Y, Sugimoto M, Usuki S, Naruse M, Murakami K, Miyazaki H. Characterization of angiotensin II receptor type 2 during differentiationand apoptosis of rat ovarian cultured granulosa cells. Biochemical and Biophysical Research Communications, 1995; 207:593-598.
34. Okamura K, Ito M, Chinushi M, Kodama M, Aizawa Y.Angiotensin 2 type 1 receptor blocker attenuates atrial structural remodeling in spontaneously hypertensive rats: Role of the suppression of atrial oxidative stress. Journal of Molecular and Cellular Cardiology, 2006; 41:1053-1054.
35. Voros S, Yang Z, Bove CM, Gilson WD, Epstein FH, French BA, Berr SS, Bishop SP, Conaway MR, Matsubara H, Carey RM, Kramer CM. Interaction between AT1 and AT2 receptors during postinfarction left ventricular remodeling, Am. J. Physiol. Heart Circ. Physiol, 2006; 290:H1004–H1010.
36. Carey RM, Jin XH, Siragy HM. Role of the angiotensin AT2 in blood pressure regulation and therapeutic implications. Am J Hypertens, 2001; 14(6pt 2):98S–102S.
37. Sanvitto GL, J?hren O, Hauser W, Saavedra JM. Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary. Am. J. Physiol, 1997; 273:E156–E163.
38. Barth SW, Gerstberger R. Differential regulation of angiotensinogen and AT1A receptor mRNA within the rat subfornical organ during dehydration. Molecular Brain Research, 1999;64:151-164.
39. Andersson B. The effects of injection of hypertonic NaCl solutions into different parts of the hypothalamus of goats. Acta Physiol Scand, 1953;28:188-201.
40. Fitzsimons JT. The physiological basis of thirst. Kidney Int, 1976;10:3-11.
41. Fitzsimons JT. Angiotensin, thirst and sodium appetite. Physiol Rev, 1998;78:583-686.
42. Epstein AN. Epilogue: Retrospect and prognosis. In: EpsteinAN, Kissileff HR, Stellar E, Eds. The Neuropsychology of Thirst: New Findings and Advances in Concepts. Washington, DC:VHWinston 1973; 315–322.
43. Fitzsimons JT. Some historical perspectives in the physiology of thirst. In: Epstein AN,Kissileff HR, Stellar E, Eds. The Neuropsychology of Thirst: New Findings and Advances in Concepts.Washington, DC: VHWinston, 1973: 3–33.
44. Johnson AK, Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms. Front. Neuroendocrinol,1997;18: 292–353.
45. Wirth JB, Epstein AN. Ontogeny of thirst in the infant rat. Am J Physiol, 1976;230:188-198
46. Xu Z, Ross MG. Appearance of mechanisms for thirst and vasopressin secretion induced by dehydration in near-term rat fetus. Develop Brain Res, 2000;121:11-18.
47. Xu Z, Calvario G, Yao J,.Ross MG, Day L. Central angiotensin induction of fetal brain c-fos expression and swallowing activity. Am J Physiol, 2001;280:R1837-1843.
48. Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BMW. Renin-angiotensin system and cardiovascular risk. Lancet, 2007;369:1208–1219.
49. Jones A, Dhamrait SS, Payne JR, et al. Genetic variants of angiotensin II receptors and cardiovascular risk in hypertension. Hypertension, 2003; 42: 500–506.
50. Jandeleit-Dahm KA, Tikellis C, Reid CM, Johnston CI,Cooper ME. Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens, 2005; 23:463–473.
51. Mao C, Wu J, Xiao D, Lv J, Ding Y, Xu Z, Zhang L. The effect of fetal and neonatal nicotine exposure on renal development of AT1 and AT2 receptors. Reprod Toxicol (2009), doi:10.1016/j.reprotox.2009.01.012.
52. Mao C, Zhang H, Xiao D, Zhu L, Ding Y, Zhang Y, Wu L, Xu Z, Zhang L.Perinatal nicotine exposure alters AT1 and AT2 receptor expression pattern in the brain of fetal and offspring rats. Brain Research, 2008; 1243:47-52.
53. Bogdarina I, Welham S, King PJ, Burns SP, Clark AJL. Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res, 2007; 100:520-526.
1. McKinley MJ, Denton DA, Ne lson JF, et al. Dehydration induces sodium depletion in rats, rabbits, and sheep. Am J Physiol Regulatory Integrative Comp Physiol, 1983; 45:R287–R292.
2. Re RN. Mechanisms of disease: local renin-angiotensin-aldosterone systems and the pathogenesis and treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med, 2004; 1(1):42-7.
3. Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev, 2006; 86(3):747-803.
4. Gottlieb HB, Ji LL, Jones H, et al. Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat. Am J Physiol Regul Integr Comp Physiol, 2006; 290:R1251-261.
5. Chatelain D, Montel V, Dickes-Coopman A, et al. Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat. Regul Pept, 2003; 110:249-255.
6. Salas SP, Giacaman A, Vio CP. Renal and Hormonal Effects of Water Deprivation in Late-Term Pregnant Rats. Hypertension, 2004; 44:334-339.
7. Deloof S, De Seze C, Montel V, et al. Effects of water deprivation on atrial natriuretic peptide secretion and density of binding sites in adrenal glands and kidneys of maternal and fetal rats in late gestation. European Journal of Endocrinology, 1999; 141:160–168.
8. Mao C, Guan J, Yuan X, et al. Got pure blood in fetal rats? Pediatric hematology and oncology, 2007; 24:457-460.
9. De Luca LA Jr., Xu Z, Schoorlemmer GHM, Thunhorst RL, Beltz TG, Menani JV,et al. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes. Am J Physiol Regulatory Integrative Comp Physiol, 2002; 282:R552–R559.
10. Makino Y, Minamino N, Kakishita E, Kangawa K, Matsuo H. Natriuretic peptides in water-deprived and in salt-loaded rats. Peptides, 1996;17:1031–1039.
11. Di Nicolantonio R, Mendelsohn FAO. Plasma renin and angiotensin in dehydrated and rehydrated rats. Am J Physiol, 1986; 250:R898–R901.
12. Israel A, Saavedra JM, Plunkett L. Water deprivation upregulates angiotensinⅡreceptors in rat anterior pituitary. Am J Physiol, 1985; 248:E264-267.
13. De Gasparo M, Catt KJ, Inagami T, et al. International union of pharmacology. XXⅡI. The angiotensinⅡreceptors. Pharmacol Rev, 2000; 52:415–472.
14. Johren O, Inagami T, Saavedra JM. AT1A, AT1B, and AT2 angiotensin II receptor subtype gene expression in rat brain. Neuroreport, 1995; 6(18):2549-52.
15. Rahman M, Kimura S, Nishiyama A, Hitomi H, Zhang G, Abe Y. Angiotensin II stimulates superoxide production via both angiotensin AT1A and AT1B receptors in mouse aorta and heart. Eur J Pharmacol, 2004; 485(1-3):243-9.
16. Schutz S, Le Moullec JM, Corvol P, Gasc JM. Early expression of all components of the renin–angiotensin system in human development. Am J Pathol, 1996; 149(6): 2067–2079.
17. Robillard JE, Page WV, Mathews MS, Schutte BC, Nuyt AM, Segar JL. Differential gene expression and regulation of renal angiotensinⅡreceptor subtypes (AT1 and AT2) during fetal life in sheep. Pediatr Res, 1995; 38:896–904.
18. Maric C, Aldred GP, Harris PJ, Alcorn D. Angiotensin II inhibits growth of cultured embryonic renomedullary interstitial cells through the AT2 receptor. Kidney Int, 1998; 53(1):92-9.
19. Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci U S A, 1995; 92(23):10663-7.
20. Shanmugam S, Llorens-Cortes C, Clauser E, Corvol P, Gasc JM. Expression of angiotensin II AT2 receptor mRNA during development of rat kidney and adrenal gland. Am J Physiol, 1995; 268(5 Pt 2):F922-30.
21. Norwood VF, Craig MR, Harris JM, Gomez RA. Differential expression of angiotensin II receptors during early renal morphogenesis. Am J Physiol, 1997; 272(2 Pt 2):R662-8.
22. Guron G, Friberg P. An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertens, 2000; 18(2):123-37.
23. Chen Y, Lasaitiene D, Friberg P. The renin-angiotensin system in kidney development. Acta Physiol Scand, 2004; 181(4):529-35.
1. Barker DJ. The fetal origins of diseases of old age. Eur.J.Clin.Nutr. 1992; 46: S3-S9
2. Barker DJ. Intrauterine programming of adult disease. Mol.Med.Today. 1995; 1: 418-423.
3. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989; 298:564–567.
4. Edwards LJ, McMillen IC. Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol 2001; 533:561–570.
5. Gilbert JS, Lang AL, Grant AR, Nijland MJ. Maternal nutrient restriction in heep: hypertension and decreased nephron number in offspring at 9 months of age. J Physiol 2005; 565:137–147.
6. Vehaskari VM, Aviles DH, Manning J. Prenatal programming of adult hypertension in the rat. Kidney Int 2001; 59:238–245.
7. Hemmings DG, Williams SJ, Davidge ST. Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy. Am J Physiol Heart Circ Physiol 2005; 289:H674–H682.
8. Alexander BT. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension 2003; 41:457–462.
9. Ortiz LA, Quan A, Zarzar F, Weinberg A, Baum M. Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension 2003; 41:328–334.
10. Franco Mdo C, Akamine EH, Di Marco GS, Casarini DE, Fortes ZB, Tostes RC, et al. NADPH oxidase and enhanced superoxide generation in intrauterine undernourished rats: involvement of the renin-angiotensin system. Cardiovasc Res 2003; 59:767–775.
11. Hadoke PW, Lindsay RS, Seckl JR, Walker BR, Kenyon CJ. Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure. J Endocrinol 2006; 188:435– 442.
12. Langley-Evans SC, Sherman RC, Welham SJ, Nwagwu MO, Gardner DS, Jackson AA. Intrauterine programming of hypertension: the role of the renin-angiotensin system. Biochem Soc Trans 1999; 27:88–93.
13. Xiao D, Xu Z, Huang X, Longo LD, Yang S, Zhang L. Prenatal gender-related nicotine exposure increases blood pressure response to angiotensinⅡin adult offspring. Hypertension 2008; 51:1239-1247.
14. Bol VV, Reusens BM, Remacle CA. of rat preadipocytes. Obesity (Silver Spring). 2008;16(12):2760-3.
15. Torre P, Ladaki C, ScirèG, Spadoni GL, Cianfarani S. Catch-up growth in body mass index is associated neither with reduced insulin sensitivity nor with altered lipid profile in children born small for gestational age. J Endocrinol Invest. 2008;31(9):760-4.
16. Dulloo AG. Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance. Best Pract Res Clin Endocrinol Metab. 2008 Feb;22(1):155-71.
17. Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D, The fetal and childhood growth of persons who develop type II diabetes. Ann. Intern. Med. 2000;133, 176–182.
18. Barker DJ, Osmond C, Forsen TJ et al. Trajectories of growth among children who have coronary events as adults. The New England Journal of Medicine. 2005; 353: 1802–1809.
19. Huxley RR, Shiell AW& Law CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature.Journal of Hypertension. 2000; 18: 815–831.
20. Li G, Bae S, Zhang L. Effect of prenatal hypoxia on heat stress-mediated cardioprotection in adult rat heart. Am J Physiol Heart Circ Physiol 2004; 286:H1712–H1719.
21. Dodic M, Samuel C, Moritz K, Wintour EM, Morgan J, Grigg L, Wong J. Impaired cardiac functional reserve and left ventricular hypertrophy in adult sheep after prenatal dexamethasone exposure. Circ Res 2001; 89:623–629.
22. Segar JL, Roghhair RD, Segar EM, Bailey MC, Scholz TD, Lamb FS. Early gestation dexamethasone alters baroreflex and vascular responses in newborn lambs before hypertension. Am J Physiol Regul Integr Comp Physiol 2006; 291:R481–R488.
23. Pechère-Bertschi A, Burnier M. Female sex hormones, salt, and blood pressure regulation.American Journal of Hypertension,2004,17(10): 994-1001.
24. Weinberg EO, Thienelt CD, Katz SE, Bartunek J, Tajima M, Rohrbach S, Douglas PS, Lorell BH. Gender differences in molecular remodeling in pressure overload hypertrophy. Journal of the American College of Cardiology, 1999, 34(1):264-273.
25. Douglas PS, Katz SE, Weinberg EO, Chen MH, Bishop SP, Lorell BH. Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload. Journal of the American College of Cardiology, 1998,32(4):1118-1125
26. Lu F, Bytautiene E, Tamayo E, Gamble P, Anderson GD, Hankins GDV, Longo M, Saade GR. Gender-specific effect of overexpression of sFlt-1 in pregnant mice on fetal programming of blood pressure in the offspring later in life. American Journal of Obstetrics and Gynecology, 2007,197(4):418.e1-418.e5.
27. Almeida JR, Mandarim-de-Lacerda CA. Overweight is gender-dependent in prenatal protein–calorie restricted adult rats acting on the blood pressure and the adverse cardiac remodeling. Life Sciences, 2005; 77(2):1307-1318.
28. Touyz RM, Endeman D, He G, Li JS, Schiffrin EL. Role of AT2 receptors in angiotensin II-stimulated contraction of small mesenteric arteries in young SHR. Hypertension. 1999;33:366–372.
29. Scheuer DA, Perrone MH. Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin. Am J Physiol. 1993;264:R917–R923.
30. Chatziantoniou C, Arendshorst WJ. Angiotensin receptor sites in renal vasculature of rats developing genetic hypertension. Am J Physiol. 1993;265:F853–F862.
31. Salas SP, Giacaman A, Vio CP. Renal and Hormonal Effects of Water Deprivation in Late-Term Pregnant Rats[J]. Hypertension, 2004,44:334-339.
32. De Luca LA Jr., Xu Z, Schoorlemmer GHM, Thunhorst RL, Beltz TG, Menani JV, et al. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes. Am J Physiol Regulatory Integrative Comp Physiol 2002; 282:R552–R559.
33. Makino Y, Minamino N, Kakishita E, Kangawa K, Matsuo H. Natriuretic peptides in water-deprived and in salt-loaded rats. Peptides 1996;17:1031–1039.
34. Gharbi N, Somody L, El Fazaa S, Kamoun A, Gauquelin-Koch G, Gharib C. Tissue norepinephrine turnover and cardiovascular responses during intermittent dehydration in the rat. Life Sciences.1999, 64(25):2401-2410.
35. Gardiner SM. Bennett T. Interactions between neural mechanisms, the renin-angiotensin system and vasopressin in the maintenance of blood pressure during water deprivation: studies in Long Evans and Brattleboro rats. Clinical Science. 1985, 68(6):647-57.
36. Gottlieb HB, Ji LL, Jones H, et al. Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat[J]. Am J Physiol Regul Integr Comp Physiol, 2006,290:R1251-261.
37. Chatelain D, Montel V, Dickes-Coopman A, et al. Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat[J]. Regul Pept, 2003,110:249-255.
38. Israel A, Saavedra JM, Plunkett L. Water deprivation upregulates angiotensinⅡreceptors in rat anterior pituitary. Am J Physiol 1985; 248:E264-267.
39. Re RN. Mechanisms of disease: local renin-angiotensin-aldosterone systems and the pathogenesis and treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2004;1(1):42-7.
40. Rockhold RW. Share L. Crofton JT. Brooks DP. Cardiovascular response to vasopressin vasopressor antagonist administration during water deprivation in the rat. Neuroendocrinology. 1984,38(2):139-44.
41. Gregory LC. Quillen EW Jr. Keil LC. Chang D. Reid IA. Effect of vasopressin blockade on blood pressure during water deprivation in intact and baroreceptor-denervated conscious dogs. American Journal of Physiology.254(4):E490-5, 1988
42. Di Nicolantonio R, Mendelsohn FAO. Plasma renin and angiotensin in dehydrated and rehydrated rats. Am J Physiol 1986; 250:R898–R901.
43. Brooks VL. Keil LC. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation. American Journal of Physiology. 1992,263(4):R762-9.
44. Ramsay DJ, Thrasher TN, and Bie P. Endocrine components of body fluid homeostasis. Comp Biochem Physiol A. 1988,90:777–780.
45. Rowland NE and Fregly MJ. Repletion of acute sodium deficit in rats drinking either low or high concentrations of sodium chloride solution. Am J Physiol Regulatory Integrative Comp Physiol.1992, 262: R419–R425.
46. McKinley MJ, Denton DA, Ne lson JF, et al. Dehydration induces sodium depletion in rats, rabbits, and sheep[J]. Am J Physiol Regulatory Integrative Comp Physiol, 1983,45:R287–R292.
47. Epstein AN. Epilogue: Retrospect and prognosis. In: EpsteinAN, Kissileff HR, Stellar E, Eds.The Neuropsychology of Thirst: New Findings and Advances in Concepts. Washington, DC:VHWinston 1973; 315–322.
48. Fitzsimons JT. Some historical perspectives in the physiology of thirst. In: Epstein AN,Kissileff HR, Stellar E, Eds. The Neuropsychology of Thirst: New Findings and Advances in Concepts.Washington, DC: VHWinston, 1973: 3–33.
49. De Luca LA Jr. Vendramini RC. Pereira DT. Colombari DA. David RB. de Paula PM. Menani JV. Water deprivation and the double- depletion hypothesis: common neural mechanisms underlie thirst and salt appetite. Brazilian Journal of Medical & Biological Research. 2007;40(5):707-12.
50. De Wardener HE and MacGregor GA. Sodium and blood pressure. Curr Opin Cardiol. 2002; 17(4): 360-367.
51. Contreras,R.J. High NaCl intake of rat dams alters maternal behavior and elevates blood pressure of adult offspring. Am J Physiol 1993;264:R296-304.
52. Xu Z, Shi L, Yao J. Central angiotensin II induced pressor responses and neural activity in utero and hypothalamic angiotensin receptors in pre-term ovine fetus. Am. J. Physiol (Heart & Circulation). 2004, 286: H1507-1514.
53. Fitzsimons JT. Angiotensin, thirst and sodium appetite. Physiol Rev 1998;78:583-686
54. Johnson AK, Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms. Front. Neuroendocrinol.18: 292–353, 1997.
55. Malvin RL, Mouw D, Vander AJ. Angiotensin: physiological role in water-deprivation-induced thirst of rats. Science. 1977,197(4299):171-3.
56. Sato MA. Yada MM. De Luca LA Jr. Antagonism of the renin-angiotensin system and water deprivation-induced NaCl intake in rats. Physiology & Behavior. 1996, 60(4):1099-104
57. Barney CC, Threatte RM, Fregly MJ. Water deprivation-induced drinking in rats: role of angiotensin II. Am J Physiol.1983,244(2):R244-8.
1. Bollag DM, Edelstein SS. Protein Methods. 2nd. New York: Wiley-Liss, Inc. 1996, 50-55.
2. Wasinger VC. Progress with gene-product mapping of the mollicutes: Mycoplasma genitalium. Electrophoresis, 1995; 16(7) : 1090-1094.
3. Kahn P. From genome to proteome: looking at a cell’s proteins. Science, 1995;270 (5235) : 369-370.
4. Swinbanks D. Government backs proteome proposal. Nature, 1995; 14: 378 (6558): 653.
5. Hochstrasser DF. Proteome in perspective. Clin Chem Lab Med, 1998; 36(11): 825-836
6. Humphery SI, Cordwell SJ, Blackstock WP. Proteome research : complementarity and limitations with respect to the RNA and DNA worlds. Electrophoresis, 1997; 18(8): 1217-1242.
7. Anderson NL, Anderson NG. Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis, 1998; 19 (11): 1853-1861.
8. Bohring C, Krause E, Habermann B, et al. Isolation and identification of sperm membrane antigens recognized by antisperm antibodies, and their possible role in immunological infertility disease. Mol Hum Reprod, 2001; 7(2): 113-118.
9. Lian Z, Wang L, Yamaga S, et al. Genomic and proteomic analysis of the myeloid differentiation program. Blood, 2001; 98(3):513-524.
10. Rattan SI, Derventzi A, Clark BF. Protein synthesis, posttranslational modifications, and aging. Ann N Y Acad Sci, 1992; 663(1):48-62
11. Rattan SI. Synthesis, modifications, and turnover of proteins during aging. Exp Gerontol, 1996; 31(1-2):33-47.
12. Gillery P, Monboisse JC, Maquart FX, et al. Aging mechanisms of proteins. Diabete Metab, 1991; 17(1):1-16.
13. Rosenberger RF. Senescence and the accumulation of abnormal proteins. Mutat Res, 1991; 256 (2-6): 255-262.
14. Lanne B, Potthast F, Hoglund A, Brockenhuus von Low enhielm H, Nystrom AC, N ilsson F, Dahllof B. Thiourea enhances mapping of the proteome from murine white adipose tissue. Proteomics, 2001; 1 (7):819- 828.
15. Rabilloud T, Adessi C, Giraudel A, Lunardi J. Improvement of the solubilization of proteins in two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis, 1997; 18(324):307-316.
[1] Fitzsimons JT. Angiotensin, Thirst, and Sodium Appetite. Physiology review, 78(3):583-686, 1998.
[2] Johnson AK, and Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms of central integration. Frontiers in Neuroendocrinology, 18(3): 292-353, 1997.
[3] Barker DJ, Bagby SP. Developmental antecedents of cardiovascular disease: a historical perspective. J Am Soc Nephrol, 16(9):2537-2544, 2005.
[4] Yzydorczyk C, Gobeil F, Cambonie G, Lahaie I, Le NL, Samarani S, Lavoie JC, Oligny L, Pladys P, Hardy P, Nuyt AM. Exaggerated vasomotor response to angiotensinⅡin rats with fetal programming of hypertension associated with exposure to a low protein diet during gestation. Am J Physiol Regul Integr Comp Physiol, 291(4):R1060-R1068, 2006.
[5] Schutz S, Le Moullec J.M, Corvol P, Gasc J.M. Early expression of all components of the renin–angiotensin system in human development. Am. J. Pathol, 149(6): 2067–2079, 1996.
[6] Butkus A, Albiston A, Alcorn D, Giles M, McCausland J, Moritz K, Zhuo J, WintourEM. Ontogeny of angiotensin II receptors, types 1 and 2, in ovine mesonephros and metanephros. Kidney Int, 52(3):628–636, 1997.
[7] Wintour EM, Alcom D, Rockell MD. Development and function of the fetal kidney. In Brace RA, ed. Fetus and Neonate, Volume IV.1997.
[8] Rawashdeh NM, Rose JC, Rogers MS, Giammattei C, Iskandar SS. Immunocytochemical localization of renin in the developing ovine fetus. Reprod Fertil Dev, 8(1):97-101, 1996.
[9] Wang J, Perez FM, and Rose JC. Developmental Changes in Renin-Containing Cells From the Ovine Fetal Kidney. J Soc Gynecol Invest, 4(4): 191-196, 1997.
[10] Moritz K, Koukoulas I, Albiston A, Wintour EM. Angiotensin II infusion to the midgestation ovine fetus: effects on the fetal kidney. Am J Physiol, 279(4 pt 2):R1290–R1297, 2000.
[11] Xu Z, Shi L, Hu F, White R, Stewart L, Yao J, In utero development of central ANG-stimulated pressor response and hypothalamic fos expression. Brain Res, 145(2):169– 176, 2003
[12] Stanley JR, Giammattei CE, Sheikh AU, Green JL, Zehnder T and Rose JC. Effects of chronic infusion of angiotensin II on renin and blood pressure in the late-gestation fetal sheep. American Journal of Obstetrics and Gynecology, 176(4): 931-937, 1997.
[13] Chen K, Carey LC, Valego NK, Liu J, Rose JC. Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep. Am J Physiol Regul Integr Comp Physiol, 289(4):R1006–14, 2005.
[14] Tower C, Baker P. The Genetics of fetal growth restriction: Implications for management. Reviews in Gynaecological and Perinatal Practice, 6 (1-2):99–105, 2006.
[15] Zhang XQ, Varner M, Dizon-Townson D, Song F, Ward K. A molecular variant of angiotensinogen is associated with idiopathic intrauterine growth restriction. Obstet Gynecol, 101(2):237–42, 2003.
[16] Robillard JE, Page WV, Mathews MS, Schutte BC, Nuyt AM, Segar JL. Differential gene expression and regulation of renal angiotensin II receptor subtypes (AT1 and AT2) during fetal life in sheep. Pediatr Res, 38(6):896–904, 1995.
[17] Hu F, Morrissey P, Yao J, Xu Z. Development of AT1 and AT2 receptors in the ovine fetal brain. Developmental Brain Research, 150(1):51– 61, 2004.
[18] Shi L, Yao J, Koos BJ, Xu Z. Induced fetal depressor or pressor responses associated with c-fos by intravenous or intracerebroventricular losartan. Developmental Brain Research, 153(1):53–60, 2004.
[19] El-Haddad MA., Ismail Y, Gayle D, and Ross MG. Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus. Am J Physiol Regul Integr Comp Physiol, 288(4): R1014–R1020, 2005.
[20] Carey RM, Jin XH, Siragy HM. Role of the angiotensin AT2 in blood pressure regulation and therapeutic implications. Am J Hypertens, 14(6 pt 2):98S–102S, 2001.
[21] Wood CE. The function of the fetal pituitary-adrenal system. In:Thorburn GD, Harding R, eds. Oxford: Oxford University Press, :351–8,1994.
[22] Challis JR, Brooks AN. Maturation and activation of hypothalamic-pituitary-adrenal function in fetal sheep. Endocr Rev, 10(2):182–204, 1989.
[23] Moritz KM, Boon WC, Wintour EM. Aldosterone secretion by the mid-gestation ovine fetus: role of the AT2 receptor. Molecular and Cellular Endocrinology. ,157(1-2): 153–160, 1999.
[24] Mann SE, Nijland MJ, and Ross MG. Fetal Absorption of Intra-Amniotic Aldosterone: Effects on Urine Composition. J Soc Gynecol Invest, 6(5):252–7, 1999.
[25] Benson CA, Wintour EM. The effect of bilateral adrenalectomy on fluid balance in the ovine fetus. J. Physiol, 489(pt 1):235–241, 1995.
[26] Cameron VA, Aitken GD, Ellmers LJ, Kennedy MA, Espiner EA. The sites of gene expression of atrial, brain, and c-type natriuretic peptide in mouse fetal development: temporal changes in embryos and placenta. Endocrinology, 137(3):817–824, 1996.
[27] Takahashi T, Allen PD, Izumo S. Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Circ Res, 71(1):9–17, 1992.
[28] Johnson DD, Tetzke TA, Cheung CY. Gene expression of atrial natriuretic factor in ovine fetal heart during development. J Soc Gynecol Invest, 1(1):14–18, 1994.
[29] Walther T. Schultheiss HP. Tschope C. Stepan H. Natriuretic peptide system in fetal heart and circulation. J Hypertens, 20(5):785–791, 2002.
[30] Cheung CY. Regulation of atrial natriuretic factor secretion and expression in the ovine fetus. Neurosci Behav Rev, 19(2):159–164, 1995.
[31] Walther T, Stepan H, Faber R. Dual natriuretic peptide response to volume load in fetal circulation. Cardiovasc Res, 49(4):817-819, 2001.
[32] Cameron VA and Ellmers LJ. Minireview: Natriuretic Peptides during Development of the Fetal Heart and Circulation. Endocrinology, 144(6):2191–2194, 2003.
[33] Lim AT, Gude NM. Atrial natriuretic factor production by the human placenta. J Clin Endocrinol Metab, 80(10):3091–3093, 1996.
[34] Dodd A, Kullama LK, Ervin MG, Leake RD, Ross MG. Ontogeny of fetal renal atrium natriuretic factor receptors. Life Sci, 54(15):1101-1107, 1994.
[35] Perreault T, Baribeau J, Gutkowska J. ANF system in the newborn piglet pulmonary vessels. J Cardiovasc Pharmacol, 29(6):740-746, 1997.
[36] Xu H. Hu XY. Wu L. Zhou JN. Neurotensin expressing neurons developed earlier than vasoactive intestinal polypeptide and vasopressin expressing neurons in the human suprachiasmatic nucleus. Neuroscience Letters, 335 (3):175–178, 2003.
[37] Lipari EF, Lipari D, Gerbino A, Di Liberto D, Bellafiore M, Catalano M, Valentino B. The hypothalamic magnocellular neurosecretory system in developing rats. Eur J Histochem, 45(2):163–168, 2001.
[38] Hansenne I. Rasier G. Pequeux C. Brilot F. Renard Ch. Breton C. Greimers R. Legros JJ. Geenen V. Martens HJ. Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network.. Journal of Neuroimmunology, 158(1-2):67– 75, 2005.
[39] Martinez A, Farr A, Vos MD, Cuttitta F, Treston AM. Peptide-amidating enzymes are expressed in the stellate epithelial cells of the thymic medulla. J. Histochem. Cytochem, 46(5):661– 668, 1998.
[40] Arnauld E, Wattiaux JP, Arsaut J, Rostene W, Vincent JD. Alterations in vasopressin and oxytocin messenger RNA in the rat supraoptic nucleus during dehydration-rehydration evaluated by in situ hybridization and northern blotting. Neurosci Lett, 149(2):177-181, 1993.
[41] Ramirez BA. Wang S. Kallichanda N. Ross MG. Chronic in utero plasma hyperosmolality alters hypothalamic arginine vasopressin synthesis and pituitary arginine vasopressin content in newborn lambs. American Journal of Obstetrics and Gynecology, 187(1):191-196, 2002.
[42] Laszlo FA, Laszlo F Jr, De Wied D. Pharmacology and clinical perspectives of vasopressin antagonists. Pharmacol Rev, 43(1):73–108, 1991.
[43] McCann SM, Antunes-Rodrigues J, Jankowski M, Gutkowska J. Oxytocin,vasopressin and atrial natriuretic peptide control body fluid homeostasis by action on their receptors in brain, cardiovascular system and kidney. Prog Brain Res, 139:309–328, 2002.
[44] Nielsen S, Chou CL, Marples D Christensen EI, Kishore BK, Knepper MA. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci USA, 92(4):1013–1017, 1995.
[45] Albuquerque CA. Nijland MJ. Ross MG. Mechanism of arginine vasopressin suppression of ovine fetal lung fluid secretion: lack of V2-receptor effect. Journal of Maternal-Fetal Medicine, 7(4):177-82, 1998.
[46] Varlinskaya EI, Petrov ES, Robinson SR, Smotherman WP. Behavioral effects of centrally administered arginine vasopressin in the rat fetus. Behavioral Neuroscience, 108(2):395-409, 1994.
[47] Xu Z, Hu F, Shi L, Morrissey P, Stewart L, Yao J. Central angiotensin-mediated vasopressin release and activation of hypothalamic neurons in younger fetus at pre-term. Peptides, 26(2):307–314, 2005.
[48] Jensen E, Wood CE, and Keller-Wood M. Alterations in Maternal Corticosteroid Levels Influence Fetal Urine and Lung Liquid Production. J Soc Gynecol Investig, 10(8):480–9, 2003.
[49] Tena JJ, Neto A, de la Calle-Mustienes E, Bras-Pereira C, Casares F, Gomez-Skarmeta JL. Odd-skipped genes encode repressors that control kidney development. Developmental Biology, 301(2):518–531, 2007.
[50] Schedl A and Hastie ND. Cross-talk in kidney development. Current Opinion in Genetics & Development, 10(5):543–549, 2000.
[51] Woolf AS, Price KL, Scambler PJ, Winyard PJ. Evolving concepts in human renal dysplasia. J Am Soc Nephrol, 15(4):998–1007, 2004.
[52] Guignard JP. Renal morphogenesis and development of renal function. In: Taeusch HW, Ballard RA, Gleason CA, editors. Avery’s diseases of the newborn. Philadelphia: Elsevier Saunders; 1258–1259, 2005.
[53] Beck JC, Lipkowitz MS, Abramson RG. Characterization of the fetal glucose transporter in rabbit kidney: comparison with the adult brush border electrogenic Na+-glucose symporter. J Clin Invest, 82(2):379–387, 1988.
[54] Igarashi P, Vanden Heuvel GB, Payne JA, and Forbush B 3rd. Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. Am J Physiol Renal Fluid Electrolyte Physiol, 269(3 pt 2):F405–F418, 1995.
[55] Quigley R, Mulder J, Baum M. Ontogeny of water transport in the rabbit proximal tubule. Pediatric Nephrology, 18(11):1089-1094, 2003.
[56] Bonilla-Felix M and Jiang W. Aquaporin-2 in the immature rat: expression, regulation and trafficking. J Am Soc Nephrol, 8(10): 1502–1509, 1997.
[57] Lumbers ER. Functions of the renin angiotensin system during development. Clin Exp Pharmacol Physiol, 22(8):499-505, 1995.
[58] Bonilla-Felix M. Development of water transport in the collecting duct. Am J Physiol Renal Physiol, 287(6): F1093–F1101, 2004.
[59] Ross MG, Kullama LK, Ogundipe OA, Chan K, Ervin MG. Ovine fetal swallowing response to intracerebroventricular hypertonic saline. J Appl Physiol, 78(6):2267–2271, 1995.
[60] El-Haddad MA, Chao CR, Sayed AA, Ross MG. Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity. Am J Obstet Gynecol,185(4):828–833, 2001.
[61] El-Haddad MA, Chao CR and Ross MG. N-Methyl-D-Aspartate Glutamate Receptor Mediates Spontaneous and Angiotensin II–Stimulated Ovine Fetal Swallowing. J Soc Gynecol Investig, 12(7):504–509, 2005.
[62] Xu Z, Nijland MJ, Ross MG. Plasma osmolality dipsogenic thresholds and c-fos expression in the near-term ovine fetus. Pediatr Res, 49(5):678–685, 2001.
[63] El-Haddad MA, Desai M, Gayle D, and Ross MG. In Utero Development of Fetal Thirst and Appetite: Potential for Programming. J Soc Gynecol Investig, 11(3):123–130, 2004.
[64] Xu Z, Glenda C, Day L. Yao J, Ross MG. Central angiotensin induction of fetal brain c-fos expression and swallowing activity. Am J Physiol Regul Integr Com, 280(6), 2005.