强的松对心力衰竭治疗中利尿剂的利尿效果的影响的研究
摘要
目的:慢性心力衰竭是一种复杂的临床症候群,是各种心脏病的最终转归。利尿剂是现代心力衰竭治疗的基石。但现有的利尿剂都是在造成肾功能进一步损害的前提下实现利尿作用的,而且在心力衰竭晚期,由于长期应用利尿剂,常造成利尿剂抵抗,使心力衰竭的治疗变得更为困难。因此,发现能在改善肾功能的同时有强大利尿作用的药物变得日益紧迫。
研究表明,糖皮质激素对肾脏有显著的生理效应。传统研究表明,糖皮质激素有致液体潴留和钠潴留的作用。因此,患者应慎用糖皮质激素。虽然这种观点在医学界广泛流行,但却缺少数据支持。事实上,一些动物试验研究表明,糖皮质激素能够扩张肾血管,调节心钠素(ANP)的合成和释放,上调血管上皮细胞上的ANP受体。因此,糖皮质激素能有效增加利尿和尿钠排泄。但是,在心力衰竭的患者中,糖皮质激素是否仍能够利尿,还不得而知。因此,我们设计了这一随机、双盲、安慰剂对照的临床研究,旨在确定强的松这种糖皮质激素,是否在充血性心力衰竭患者中具有利尿作用。
方法:2005年11月至2006年4月期间,我们征集了在心内科住院治疗的20位心力衰竭患者,符合纽约心脏病协会(NYHA)分级Ⅱ~Ⅲ级,20例患者中男性11例,女性9例,年龄30~72岁,平均年龄57.6±10.2岁。并除外存在感染、患糖尿病、患急性冠脉综合征、存在难以控制的高血压、活动性消化性溃疡、新近胃肠吻合术、创伤修复期、孕妇及哺乳期妇女、肾上腺皮质功能亢进症、曾患或现患严重精神病和癫痫、恶性肿瘤及其他威胁生命的疾病者。所有患者入选前均接受常规治疗,有正常的肾上腺皮质功能、应用利尿剂治疗、临床稳定、至少连续3天体重保持不变,没有明显的液体潴留体征。根据电脑生成的随机数字,我们将受试者随机分入强的松组(入选10例,其中男性7例,女性3例,平均年龄45±14.4岁)或安慰剂组(入选10例,其中男性4例,女性6例,平均年龄51±10.7岁)。遵循双盲原则,试验组应用强的松(1 mg/kg/d,最大剂量为60 mg/d),同时给予标准化治疗7天。对照组给予安慰剂,同时保持其他药物治疗不变,尤其是利尿剂的种类和剂量保持不变。
收集每个患者24小时尿量,连续7天。检测24小时尿电解质(尿钾、钠、氯)和肌酐含量的变化情况。同时监测试验开始前(第一天服药前)和结束后(第八天)患者血清电解质和肌酐浓度的变化。我们于每日清晨7:00~8:00之间采血,采血时患者取平卧位,休息15分钟以上,采集肘正中静脉血4ml以XL-20型自动生化分析仪进行检测。并记录每日体重以监测患者体内液体容量变化情况。
所有数据输入SPSS13.0统计软件包进行统计,计量资料用均数±标准差表示,组间比较采用Mann-Whitney U检验和t检验,组内治疗前后比较采用Wilcoxon符号秩检验,计数资料采用χ2检验。P<0.05表示统计学有显著性差异。
结果:两组间治疗前基本临床情况包括:年龄、性别、体重、心率、血压、导致心衰的原因、左心室功能障碍的程度、药物治疗情况、电解质情况以及肾功能情况(见附表1)。两组数据均衡,无统计学差异(P值均>0.05),具有可比性。
试验组加用强的松后,尿量和尿钠排泄量随时间显著增加。与安慰剂组相比,试验组平均每天尿量最大值比安慰剂组高出810.5毫升,差异性显著(95%可信区间为276.25至1344.86,P< 0.05)。最大日平均尿钠排泄量高于安慰剂组患者123.8 mmol,差异性显著(95%可信区间为11.4至236.2,P< 0.05)。与基线水平相比,经安慰剂组校正后,治疗组血清肌酐减少了19.5μmol/L (95%可信限为–7.4~ -31.6, P<0.01),显示强的松可以改善肾功能。与安慰剂组相比,强的松组的患者体重轻微减轻,然而这种差异没有明显的统计学意义(P>0.05)。
结论:这项初步研究表明强的松在心衰患者中能够增加尿量,促进尿钠和尿氯的排泄,有效增强利尿剂效果,但对尿钾无明显影响;能够促进肌酐的排泄,改善肾功能;而且对患者血清电解质没有明显的影响,没有发生严重的不良反应。限于本试验的样本量较小,有待于多中心、随机的、大规模的临床试验进一步的证实,同时,糖皮质激素是否对失代偿性充血性心力衰竭仍有利尿作用,尚需进行进一步的前瞻性随机临床研究。同时,糖皮质激素有效剂量和有效性也需进一步评价。
Objective:Chronic heart failure is a cluster of complicated clinical symptomatic syndrome. It is the severe end stage of all kinds of heart diseases. The basis of treating for heart failure in modern time is diuretic.But the forthcoming diuretic implement diuresis by more lesion of renal function.Forthermore,at the end of heart failure,as the application of diuretic for long time usually result in antidiuretic,the treatment of heart hailure become more difficult.So it’s urgent to find a drug which can not only improve renal function,but also play a important role for powerful diuresis. Glucocorticoids are known to have pronounced physiological effects in kidney. Conventional teaching dictates that it should be used with caution in congestive heart failure(CHF)patients, due to its fluid and sodium retention effects. Surprisingly, despite the widespread prevalence of this belief within the medical community, there are few data to support it. In fact, animal studies showed glucocorticoids could specifically dilate renal vasculature, regulate synthesis and release of natriuretic peptide (ANP), upregulate ANP receptors on vascular endothelial cells thus have potent potentiating diuresis and natriuresis effects in animal studies, their diuretic efficacy in human yet to be known. Thus, we designed this randomized, double blind, placebo controlled, clinical study to determine the diuretic efficacy of prednisone, a glucocorticoid, in patients with CHF.
Methods:Twenty clinically stable CHF patients without overt fluid retention (11 men and 9 women,age from 30 to 72,mean age 57.6±10.2 years) who had New York Heart Association (NYHA) classⅡ~Ⅲ( with normal cortical function, on diuretic therapy, and being clinically stable and whose body weight maintained the same for at least 3 days without overt signs of fluid retention )were randomized to prednisone group(in all 10 patients,7 male and 3 female,with mean age of 45±14.4 years) or placebo group(in all 10 patients,4 male and 6 female,with mean age of 51±10.7 years)between November 2005 and April 2006. Exclusion Criteria were patient refusal and having signs of infection, diabetes mellitus, acute coronary syndrome,uncontrolled hypertension,reactiveness peptic ulcer, recent gastrointestinal anastomosis,repairing in trauma, adrenocortical hyperfunction, worrying cacopathia and epilepsy ,malignant tumor, pregnancy or breastfeeding women,and life-threaten disease. Prednisone (1 mg/kg/day with maximum dose of 60 mg/day) was added to standard care for 7 days, leaving other medications unchanged,especially the diuretic. Variables included urine volume and electrolytes, serum electrolytes, and change from baseline in serum creatinine.
All statistical tests were performed with two-sided alternatives and a typeⅠerror of 0.05 and with the use of SPSS software(version13.0).Initially the homogeneity of variance among all the groups was analyzed. All the measurement data was expressed as mean±standard deviation(mean±SD) unless otherwise stated. Mann-Whitney U test and student t test was used to analyze differences of parameters between two treatment groups. Chi-square test was used for analysis of categorical data.The other used compared two samples wilcoxon rank sum test.
Results:The two groups of patients were well matched with regard to baseline characteristics of age, sex,weight,heart rate,blood pressure,etiology of heart failure, severity of left ventricle dysfunction, medical therapy, electrolyte status, and renal function (P>0.05)(table 1).
Adding prednisone resulted in striking diuresis and natriuresis with time. As compared with placebo group, the maximum of mean daily urine volume was 810.5 ml larger than those in placebo group (95% confidence intervals [CI] 276.25 to 1344.86, P< 0.05). The maximum mean daily sodium excretion was 123.8 mmol higher than those patients given placebo (95% CI 11.4 to 236.2, P< 0.05). The placebo-corrected effect on change from baseline in serum creatinine was -19.5μmol/L (95% CI–7.4 to -31.6, P<0.01), favoring prednisone.It appeared that prednisone can improve renal function,comparing with the placobo,the patients of prednisone lost weight a little.But there were no significant differences between two groups.
Conclusion:This pilot study showed that prednisone can increase urine volume,promote diuresis and natriuresis, had potent potentiating diuretic effects,but had no effects on urine potassium in patients with heart failure, promote the excretion of urine creatinine and might improve renal function in the same time,had no effects on serum electrolytes,and there were no serious adverse effect. Due to the sample size is small,we need multicenter,random,large scale clinical test to confirm nextly.Further prospective randomized clinical studies are warranted to determine the preferable dose and its efficacy in decompensated congestive heart failure.
研究表明,糖皮质激素对肾脏有显著的生理效应。传统研究表明,糖皮质激素有致液体潴留和钠潴留的作用。因此,患者应慎用糖皮质激素。虽然这种观点在医学界广泛流行,但却缺少数据支持。事实上,一些动物试验研究表明,糖皮质激素能够扩张肾血管,调节心钠素(ANP)的合成和释放,上调血管上皮细胞上的ANP受体。因此,糖皮质激素能有效增加利尿和尿钠排泄。但是,在心力衰竭的患者中,糖皮质激素是否仍能够利尿,还不得而知。因此,我们设计了这一随机、双盲、安慰剂对照的临床研究,旨在确定强的松这种糖皮质激素,是否在充血性心力衰竭患者中具有利尿作用。
方法:2005年11月至2006年4月期间,我们征集了在心内科住院治疗的20位心力衰竭患者,符合纽约心脏病协会(NYHA)分级Ⅱ~Ⅲ级,20例患者中男性11例,女性9例,年龄30~72岁,平均年龄57.6±10.2岁。并除外存在感染、患糖尿病、患急性冠脉综合征、存在难以控制的高血压、活动性消化性溃疡、新近胃肠吻合术、创伤修复期、孕妇及哺乳期妇女、肾上腺皮质功能亢进症、曾患或现患严重精神病和癫痫、恶性肿瘤及其他威胁生命的疾病者。所有患者入选前均接受常规治疗,有正常的肾上腺皮质功能、应用利尿剂治疗、临床稳定、至少连续3天体重保持不变,没有明显的液体潴留体征。根据电脑生成的随机数字,我们将受试者随机分入强的松组(入选10例,其中男性7例,女性3例,平均年龄45±14.4岁)或安慰剂组(入选10例,其中男性4例,女性6例,平均年龄51±10.7岁)。遵循双盲原则,试验组应用强的松(1 mg/kg/d,最大剂量为60 mg/d),同时给予标准化治疗7天。对照组给予安慰剂,同时保持其他药物治疗不变,尤其是利尿剂的种类和剂量保持不变。
收集每个患者24小时尿量,连续7天。检测24小时尿电解质(尿钾、钠、氯)和肌酐含量的变化情况。同时监测试验开始前(第一天服药前)和结束后(第八天)患者血清电解质和肌酐浓度的变化。我们于每日清晨7:00~8:00之间采血,采血时患者取平卧位,休息15分钟以上,采集肘正中静脉血4ml以XL-20型自动生化分析仪进行检测。并记录每日体重以监测患者体内液体容量变化情况。
所有数据输入SPSS13.0统计软件包进行统计,计量资料用均数±标准差表示,组间比较采用Mann-Whitney U检验和t检验,组内治疗前后比较采用Wilcoxon符号秩检验,计数资料采用χ2检验。P<0.05表示统计学有显著性差异。
结果:两组间治疗前基本临床情况包括:年龄、性别、体重、心率、血压、导致心衰的原因、左心室功能障碍的程度、药物治疗情况、电解质情况以及肾功能情况(见附表1)。两组数据均衡,无统计学差异(P值均>0.05),具有可比性。
试验组加用强的松后,尿量和尿钠排泄量随时间显著增加。与安慰剂组相比,试验组平均每天尿量最大值比安慰剂组高出810.5毫升,差异性显著(95%可信区间为276.25至1344.86,P< 0.05)。最大日平均尿钠排泄量高于安慰剂组患者123.8 mmol,差异性显著(95%可信区间为11.4至236.2,P< 0.05)。与基线水平相比,经安慰剂组校正后,治疗组血清肌酐减少了19.5μmol/L (95%可信限为–7.4~ -31.6, P<0.01),显示强的松可以改善肾功能。与安慰剂组相比,强的松组的患者体重轻微减轻,然而这种差异没有明显的统计学意义(P>0.05)。
结论:这项初步研究表明强的松在心衰患者中能够增加尿量,促进尿钠和尿氯的排泄,有效增强利尿剂效果,但对尿钾无明显影响;能够促进肌酐的排泄,改善肾功能;而且对患者血清电解质没有明显的影响,没有发生严重的不良反应。限于本试验的样本量较小,有待于多中心、随机的、大规模的临床试验进一步的证实,同时,糖皮质激素是否对失代偿性充血性心力衰竭仍有利尿作用,尚需进行进一步的前瞻性随机临床研究。同时,糖皮质激素有效剂量和有效性也需进一步评价。
Objective:Chronic heart failure is a cluster of complicated clinical symptomatic syndrome. It is the severe end stage of all kinds of heart diseases. The basis of treating for heart failure in modern time is diuretic.But the forthcoming diuretic implement diuresis by more lesion of renal function.Forthermore,at the end of heart failure,as the application of diuretic for long time usually result in antidiuretic,the treatment of heart hailure become more difficult.So it’s urgent to find a drug which can not only improve renal function,but also play a important role for powerful diuresis. Glucocorticoids are known to have pronounced physiological effects in kidney. Conventional teaching dictates that it should be used with caution in congestive heart failure(CHF)patients, due to its fluid and sodium retention effects. Surprisingly, despite the widespread prevalence of this belief within the medical community, there are few data to support it. In fact, animal studies showed glucocorticoids could specifically dilate renal vasculature, regulate synthesis and release of natriuretic peptide (ANP), upregulate ANP receptors on vascular endothelial cells thus have potent potentiating diuresis and natriuresis effects in animal studies, their diuretic efficacy in human yet to be known. Thus, we designed this randomized, double blind, placebo controlled, clinical study to determine the diuretic efficacy of prednisone, a glucocorticoid, in patients with CHF.
Methods:Twenty clinically stable CHF patients without overt fluid retention (11 men and 9 women,age from 30 to 72,mean age 57.6±10.2 years) who had New York Heart Association (NYHA) classⅡ~Ⅲ( with normal cortical function, on diuretic therapy, and being clinically stable and whose body weight maintained the same for at least 3 days without overt signs of fluid retention )were randomized to prednisone group(in all 10 patients,7 male and 3 female,with mean age of 45±14.4 years) or placebo group(in all 10 patients,4 male and 6 female,with mean age of 51±10.7 years)between November 2005 and April 2006. Exclusion Criteria were patient refusal and having signs of infection, diabetes mellitus, acute coronary syndrome,uncontrolled hypertension,reactiveness peptic ulcer, recent gastrointestinal anastomosis,repairing in trauma, adrenocortical hyperfunction, worrying cacopathia and epilepsy ,malignant tumor, pregnancy or breastfeeding women,and life-threaten disease. Prednisone (1 mg/kg/day with maximum dose of 60 mg/day) was added to standard care for 7 days, leaving other medications unchanged,especially the diuretic. Variables included urine volume and electrolytes, serum electrolytes, and change from baseline in serum creatinine.
All statistical tests were performed with two-sided alternatives and a typeⅠerror of 0.05 and with the use of SPSS software(version13.0).Initially the homogeneity of variance among all the groups was analyzed. All the measurement data was expressed as mean±standard deviation(mean±SD) unless otherwise stated. Mann-Whitney U test and student t test was used to analyze differences of parameters between two treatment groups. Chi-square test was used for analysis of categorical data.The other used compared two samples wilcoxon rank sum test.
Results:The two groups of patients were well matched with regard to baseline characteristics of age, sex,weight,heart rate,blood pressure,etiology of heart failure, severity of left ventricle dysfunction, medical therapy, electrolyte status, and renal function (P>0.05)(table 1).
Adding prednisone resulted in striking diuresis and natriuresis with time. As compared with placebo group, the maximum of mean daily urine volume was 810.5 ml larger than those in placebo group (95% confidence intervals [CI] 276.25 to 1344.86, P< 0.05). The maximum mean daily sodium excretion was 123.8 mmol higher than those patients given placebo (95% CI 11.4 to 236.2, P< 0.05). The placebo-corrected effect on change from baseline in serum creatinine was -19.5μmol/L (95% CI–7.4 to -31.6, P<0.01), favoring prednisone.It appeared that prednisone can improve renal function,comparing with the placobo,the patients of prednisone lost weight a little.But there were no significant differences between two groups.
Conclusion:This pilot study showed that prednisone can increase urine volume,promote diuresis and natriuresis, had potent potentiating diuretic effects,but had no effects on urine potassium in patients with heart failure, promote the excretion of urine creatinine and might improve renal function in the same time,had no effects on serum electrolytes,and there were no serious adverse effect. Due to the sample size is small,we need multicenter,random,large scale clinical test to confirm nextly.Further prospective randomized clinical studies are warranted to determine the preferable dose and its efficacy in decompensated congestive heart failure.
引文
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24 Hughes JM, Beck TR, Rose CE, Jr., Carey RM. The effect of selective dopamine-1 receptor stimulation on renal and adrenal function in man. J Clin Endocrinol Metab 1988;66(3):518~25
25 Hughes JM, Ragsdale NV, Felder RA, Chevalier RL, King B, Carey RM. Diuresis and natriuresis during continuous dopamine-1 receptor stimulation. Hypertension 1988;11(2 Pt 2):I69~74
26 Ragsdale N, Lynd M, Chevalier R, Felder R, Peach M, Carey R. Selective peripheral dopamine-1 receptor stimulation. Differential responses to sodium loading and depletion in humans. Hypertension 1990;15(6):914~921
27 Cooper CL, Malik KU. Effect of glucocorticoids on vascular reactivity to vasoactive hormones in rat isolated kidney: lack of relationship to prostaglandins. Br J Pharmacol 1984;82(3):679~88
28 Radermacher J, Forstermann U, Frolich JC. Endothelium-derived relaxing factor influences renal vascular resistance. Am J Physiol 1990;259(1 Pt 2):F9~17
29 Tolins J, Shultz P, Raij L. Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. Hypertension 1991;17(6):909~916
30 Edwards RM. Effects of prostaglandins on vasoconstrictor action in isolated renal arterioles. Am J Physiol Renal Physiol 1985;248(6):F779~784
31 de Matteo R, May CN. Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep. Am J Physiol Regul Integr Comp Physiol 1999;276(4):R1125~1131
32 Bobadilla NA, Tapia E, Jimenez F, Sanchez-Lozada LG, Santamaria J, Monjardin A, et al. Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin. Am J Physiol Renal Physiol 1999;277(3):F464~471
1 许顶立,任昊.慢性心力衰竭水潴留机制的研究进展.第一军医大学学报,2001,21:65~67
2 Schrier RW ,Abraham WT.Hormones and hemodynamics in heart failure.N Engl J Med 1999;341:577~585
3 Peters JP. The role of sodium in the production of edema.N Engl J Med 1948;239:353~362
4 Cadnapaphornchai MA , Gurevich AK , Weinberger HD,Schrier RW.Pathophysiology of sodium and water retention in heart failure.Cardiology 2001;96:122~131
5 Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure,nephritic syndrome,cirrhosis,and pregnancy.N Engl J Med 1988;319:1065~1072
6 Myers GL, Miller WG, Coresh J, et al. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.Clin Chem 2006;52:5~18
7 Sica DA, Gehr TW. Diuretic combinations in refractory oedema states : pharmacokinetic – pharmacodynamic relationships.Clin Pharmacokinet 1996;30:229~249
8 Mclay JS, McMurry JJ, Bridges A B, Fraser CG, Struthers AD. Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure.Am Heart J 1993;126:879~886
9 Francis GS , Siegel RM, Goldsmith SR ,Olivari MT, Levine TB, Cohn JN. Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure.Activation of the neurohumoral axis.Ann Intern Med 1985;103:1~6
10 Hall JE, Brands MW, Henegar JR. Angiotensin Ⅱ and long-term arterial pressure regulation:the overriding dominance of the kidney. J Am Soc Nephrol 1999;10(Suppl 12):S258~S265
11 Burns KD, Li N. The role of angiotensin Ⅱ-stimulated renal tubular transport in hypertension.Curr Hypertens Rep2003;5:165~171
12 Eiskjaer H, Bagger JP, Danielsen H, et al. Mechanisms of sodium retention in heart failure:relation to the rennin-angiotensin-aldosterone system.Am J Physiol 1991;260:F883~F889
13 Schoolwerth A, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin-converting enzyme inhibitor therapy. A Statement for Healthcare Professionals From the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association.Circulation2001;104:1985~1991
14 Sica DA. Hyponatremia and heartfailure pathophysiology and implications.Congest Heart Fail 2005;11:274~277
15 Baylis C, Handa RK, Sorkin M. Glucocorticoids and control of glomerular filtration rate. Semin Nephrol 1990;10(4):320~9
16 Baylis C, Brenner BM. Mechanism of the glucocorticoid-induced increase in glomerular filtration rate. Am J Physiol 1978;234(2):F166~70
17 Carey RM. Renal Dopamine System: Paracrine Regulator of Sodium Homeostasis and Blood Pressure Hypertension 2001;38(3):297~302
18 Zeng C, Asico LD, Wang X, Hopfer U, Eisner GM, Felder RA, et al. Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR. Hypertension 2003;41(3 Pt 2):724~9
19 Zeng C, Yang Z, Wang Z, Jones J, Wang X, Altea J, et al. Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. Hypertension 2005;45(4):804~10
20 Zeng C, Liu Y, Wang Z, He D, Huang L, Yu P, et al. Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells. Circ Res 2006;99(5):494~500
21 Hall JE, Brands MW, Henegar JR. Angiotensin II and long-term arterial pressure regulation: the overriding dominance of the kidney. J Am Soc Nephrol 1999;10 Suppl 12:S258~65
22 Ardaillou R, Chansel D. Glomerular effects of angiotensin II: a reappraisal based on studies with non-peptide receptor antagonists. J Hypertens Suppl 1993;11(3):S43~7
23 Cheng HF, Becker BN, Harris RC. Dopamine decreases expression of type-1 angiotensin II receptors in renal proximal tubule. J Clin Invest 1996;97(12):2745~52
24 Lee MR. Dopamine and the kidney: ten years on. Clin Sci (Lond) 1993;84(4):357~75
25 Aguirre JA, Ibarra FR, Barontini M, Arrizurieta EE, Armando I. Effect of glucocorticoids on renal dopamine production. Eur J Pharmacol 1999;370(3):271~8
26 Hughes JM, Beck TR, Rose CE, Jr., Carey RM. The effect of selective dopamine-1 receptor stimulation on renal and adrenal function in man. J Clin Endocrinol Metab 1988;66(3):518~25
27 Hughes JM, Ragsdale NV, Felder RA, Chevalier RL, King B, Carey RM. Diuresis and natriuresis during continuous dopamine-1 receptor stimulation. Hypertension 1988;11(2 Pt 2):I69~74
28 Ragsdale N, Lynd M, Chevalier R, Felder R, Peach M, Carey R. Selective peripheral dopamine-1 receptor stimulation. Differential responses to sodium loading and depletion in humans. Hypertension 1990;15(6):914~921
29 Cooper CL, Malik KU. Effect of glucocorticoids on vascular reactivity to vasoactive hormones in rat isolated kidney: lack of relationship to prostaglandins. Br J Pharmacol 1984;82(3):679~88
30 Garcia R, Debinski W, Gutkowska J, Kuchel O, Thibault G, Genest J, et al. Gluco- and mineralocorticoids may regulate the natriuretic effect and the synthesis and release of atrial natriuretic factor by the rat atria in vivo. Biochem Biophys Res Commun 1985;131(2):806~14
31 Lanier-Smith KL, Currie MG. Effect of glucocorticoids on the binding of atrial natriuretic peptide to endothelial cells. Eur J Pharmacol 1990;178(1):105~9
32 Kanda K, Ogawa K, Miyamoto N, Hatano T, Seo H, Matsui N. Potentiation of atrial natriuretic peptide-stimulated cyclic guanosine monophosphate formation by glucocorticoids in cultured rat renal cells. Br J Pharmacol 1989;96(4):795~800
33 Damjancic P, Vierhapper H. Permissive action of glucocorticoid substitution therapy on the effects of atrial natriuretic peptide (hANP) in patients with adrenocortical insufficiency. Exp Clin Endocrinol 1990;95(3):315~21
34 Radermacher J, Forstermann U, Frolich JC. Endothelium-derived relaxing factor influences renal vascular resistance. Am J Physiol 1990;259(1 Pt 2):F9~17
35 Tolins J, Shultz P, Raij L. Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. Hypertension 1991;17(6):909~916
36 Edwards RM. Effects of prostaglandins on vasoconstrictor action in isolated renal arterioles. Am J Physiol Renal Physiol 1985;248(6):F779~784
37 De Matteo R, May CN. Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep. Am J Physiol Regul Integr Comp Physiol 1999;276(4):R1125~1131
38 Bobadilla NA, Tapia E, Jimenez F, Sanchez-Lozada LG, Santamaria J, Monjardin A, et al. Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin. Am J Physiol Renal Physiol 1999;277(3):F464~471
2 Garcia R, Debinski W, Gutkowska J, et al. Gluco- and mineralocorticoids may regulate the natriuretic effect and the synthesis and release of atrial natriuretic factor by the rat atria in vivo. Biochem Biophys Res Commun 1985;131(2):806~14
3 May CN, Bednarik JA. Regional hemodynamic and endocrine effects of aldosterone and cortisol in conscious sheep. Comparison with the effects of corticotropin. Hypertension 1995;26(2):294 ~300
4 Baylis C, Brenner BM. Mechanism of the glucocorticoid-induced increase in glomerular filtration rate. Am J Physiol 1978;234(2):F166~70
5 卢亮,厉伟民.肾上腺皮质功能变化在顽固性充血性心力衰竭患者中的临床意义.中国危重病急救医学.2003,15(8):489~491
6 De Matteo R, May CN. Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide. Am J Physiol 1997;273(6 Pt 2):R1972~9
7 Aguirre JA, Ibarra FR, Barontini M, Arrizurieta EE, Armando I. Effect of glucocorticoids on renal dopamine production. Eur J Pharmacol 1999;370(3):271~8
8 Garcia R, Debinski W, Gutkowska J, Kuchel O, Thibault G, Genest J, et al. Gluco- and mineralocorticoids may regulate the natriuretic effect and the synthesis and release of atrial natriuretic factor by the rat atria in vivo. Biochem Biophys Res Commun 1985;131(2):806~14
9 Lanier-Smith KL, Currie MG. Effect of glucocorticoids on the binding of atrial natriuretic peptide to endothelial cells. Eur J Pharmacol 1990;178(1):105~9
10 Kanda K, Ogawa K, Miyamoto N, Hatano T, Seo H, Matsui N. Potentiation of atrial natriuretic peptide-stimulated cyclic guanosine monophosphate formation by glucocorticoids in cultured rat renal cells. Br J Pharmacol 1989;96(4):795~800
11 Damjancic P, Vierhapper H. Permissive action of glucocorticoid substitution therapy on the effects of atrial natriuretic peptide (hANP) in patients with adrenocortical insufficiency. Exp Clin Endocrinol 1990;95(3):315~21
12 Nevskaia TL, Shcherbinina AV, Ivanov Iu I. [Effect of glucocorticoids on electrolyte excretion after expansion of the extracellular space]. Probl Endokrinol (Mosk) 1977;23(6):48~51
13 Baylis C, Handa RK, Sorkin M. Glucocorticoids and control of glomerular filtration rate. Semin Nephrol 1990;10(4):320~9
14 Baylis C, Brenner BM. Mechanism of the glucocorticoid-induced increase in glomerular filtration rate. Am J Physiol 1978;234(2):F166~70
15 Carey RM. Renal Dopamine System: Paracrine Regulator of Sodium Homeostasis and Blood Pressure Hypertension 2001;38(3):297~302
16 Zeng C, Asico LD, Wang X, Hopfer U, Eisner GM, Felder RA, et al. Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR. Hypertension 2003;41(3 Pt 2):724~9
17 Zeng C, Yang Z, Wang Z, Jones J, Wang X, Altea J, et al. Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. Hypertension 2005;45(4):804~10
18 Zeng C, Liu Y, Wang Z, He D, Huang L, Yu P, et al. Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells. Circ Res 2006;99(5):494~500
19 Hall JE, Brands MW, Henegar JR. Angiotensin II and long-term arterial pressure regulation: the overriding dominance of the kidney. J Am Soc Nephrol 1999;10 Suppl 12:S258~65
20 Ardaillou R, Chansel D. Glomerular effects of angiotensin II: a reappraisal based on studies with non-peptide receptor antagonists. J Hypertens Suppl 1993;11(3):S43~7
21 Cheng HF, Becker BN, Harris RC. Dopamine decreases expression of type-1 angiotensin II receptors in renal proximal tubule. J Clin Invest 1996;97(12):2745~52
22 Lee MR. Dopamine and the kidney: ten years on. Clin Sci (Lond) 1993;84(4):357~75
23 Aguirre JA, Ibarra FR, Barontini M, Arrizurieta EE, Armando I. Effect of glucocorticoids on renal dopamine production. Eur J Pharmacol 1999;370(3):271~8
24 Hughes JM, Beck TR, Rose CE, Jr., Carey RM. The effect of selective dopamine-1 receptor stimulation on renal and adrenal function in man. J Clin Endocrinol Metab 1988;66(3):518~25
25 Hughes JM, Ragsdale NV, Felder RA, Chevalier RL, King B, Carey RM. Diuresis and natriuresis during continuous dopamine-1 receptor stimulation. Hypertension 1988;11(2 Pt 2):I69~74
26 Ragsdale N, Lynd M, Chevalier R, Felder R, Peach M, Carey R. Selective peripheral dopamine-1 receptor stimulation. Differential responses to sodium loading and depletion in humans. Hypertension 1990;15(6):914~921
27 Cooper CL, Malik KU. Effect of glucocorticoids on vascular reactivity to vasoactive hormones in rat isolated kidney: lack of relationship to prostaglandins. Br J Pharmacol 1984;82(3):679~88
28 Radermacher J, Forstermann U, Frolich JC. Endothelium-derived relaxing factor influences renal vascular resistance. Am J Physiol 1990;259(1 Pt 2):F9~17
29 Tolins J, Shultz P, Raij L. Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. Hypertension 1991;17(6):909~916
30 Edwards RM. Effects of prostaglandins on vasoconstrictor action in isolated renal arterioles. Am J Physiol Renal Physiol 1985;248(6):F779~784
31 de Matteo R, May CN. Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep. Am J Physiol Regul Integr Comp Physiol 1999;276(4):R1125~1131
32 Bobadilla NA, Tapia E, Jimenez F, Sanchez-Lozada LG, Santamaria J, Monjardin A, et al. Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin. Am J Physiol Renal Physiol 1999;277(3):F464~471
1 许顶立,任昊.慢性心力衰竭水潴留机制的研究进展.第一军医大学学报,2001,21:65~67
2 Schrier RW ,Abraham WT.Hormones and hemodynamics in heart failure.N Engl J Med 1999;341:577~585
3 Peters JP. The role of sodium in the production of edema.N Engl J Med 1948;239:353~362
4 Cadnapaphornchai MA , Gurevich AK , Weinberger HD,Schrier RW.Pathophysiology of sodium and water retention in heart failure.Cardiology 2001;96:122~131
5 Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure,nephritic syndrome,cirrhosis,and pregnancy.N Engl J Med 1988;319:1065~1072
6 Myers GL, Miller WG, Coresh J, et al. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.Clin Chem 2006;52:5~18
7 Sica DA, Gehr TW. Diuretic combinations in refractory oedema states : pharmacokinetic – pharmacodynamic relationships.Clin Pharmacokinet 1996;30:229~249
8 Mclay JS, McMurry JJ, Bridges A B, Fraser CG, Struthers AD. Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure.Am Heart J 1993;126:879~886
9 Francis GS , Siegel RM, Goldsmith SR ,Olivari MT, Levine TB, Cohn JN. Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure.Activation of the neurohumoral axis.Ann Intern Med 1985;103:1~6
10 Hall JE, Brands MW, Henegar JR. Angiotensin Ⅱ and long-term arterial pressure regulation:the overriding dominance of the kidney. J Am Soc Nephrol 1999;10(Suppl 12):S258~S265
11 Burns KD, Li N. The role of angiotensin Ⅱ-stimulated renal tubular transport in hypertension.Curr Hypertens Rep2003;5:165~171
12 Eiskjaer H, Bagger JP, Danielsen H, et al. Mechanisms of sodium retention in heart failure:relation to the rennin-angiotensin-aldosterone system.Am J Physiol 1991;260:F883~F889
13 Schoolwerth A, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin-converting enzyme inhibitor therapy. A Statement for Healthcare Professionals From the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association.Circulation2001;104:1985~1991
14 Sica DA. Hyponatremia and heartfailure pathophysiology and implications.Congest Heart Fail 2005;11:274~277
15 Baylis C, Handa RK, Sorkin M. Glucocorticoids and control of glomerular filtration rate. Semin Nephrol 1990;10(4):320~9
16 Baylis C, Brenner BM. Mechanism of the glucocorticoid-induced increase in glomerular filtration rate. Am J Physiol 1978;234(2):F166~70
17 Carey RM. Renal Dopamine System: Paracrine Regulator of Sodium Homeostasis and Blood Pressure Hypertension 2001;38(3):297~302
18 Zeng C, Asico LD, Wang X, Hopfer U, Eisner GM, Felder RA, et al. Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR. Hypertension 2003;41(3 Pt 2):724~9
19 Zeng C, Yang Z, Wang Z, Jones J, Wang X, Altea J, et al. Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. Hypertension 2005;45(4):804~10
20 Zeng C, Liu Y, Wang Z, He D, Huang L, Yu P, et al. Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells. Circ Res 2006;99(5):494~500
21 Hall JE, Brands MW, Henegar JR. Angiotensin II and long-term arterial pressure regulation: the overriding dominance of the kidney. J Am Soc Nephrol 1999;10 Suppl 12:S258~65
22 Ardaillou R, Chansel D. Glomerular effects of angiotensin II: a reappraisal based on studies with non-peptide receptor antagonists. J Hypertens Suppl 1993;11(3):S43~7
23 Cheng HF, Becker BN, Harris RC. Dopamine decreases expression of type-1 angiotensin II receptors in renal proximal tubule. J Clin Invest 1996;97(12):2745~52
24 Lee MR. Dopamine and the kidney: ten years on. Clin Sci (Lond) 1993;84(4):357~75
25 Aguirre JA, Ibarra FR, Barontini M, Arrizurieta EE, Armando I. Effect of glucocorticoids on renal dopamine production. Eur J Pharmacol 1999;370(3):271~8
26 Hughes JM, Beck TR, Rose CE, Jr., Carey RM. The effect of selective dopamine-1 receptor stimulation on renal and adrenal function in man. J Clin Endocrinol Metab 1988;66(3):518~25
27 Hughes JM, Ragsdale NV, Felder RA, Chevalier RL, King B, Carey RM. Diuresis and natriuresis during continuous dopamine-1 receptor stimulation. Hypertension 1988;11(2 Pt 2):I69~74
28 Ragsdale N, Lynd M, Chevalier R, Felder R, Peach M, Carey R. Selective peripheral dopamine-1 receptor stimulation. Differential responses to sodium loading and depletion in humans. Hypertension 1990;15(6):914~921
29 Cooper CL, Malik KU. Effect of glucocorticoids on vascular reactivity to vasoactive hormones in rat isolated kidney: lack of relationship to prostaglandins. Br J Pharmacol 1984;82(3):679~88
30 Garcia R, Debinski W, Gutkowska J, Kuchel O, Thibault G, Genest J, et al. Gluco- and mineralocorticoids may regulate the natriuretic effect and the synthesis and release of atrial natriuretic factor by the rat atria in vivo. Biochem Biophys Res Commun 1985;131(2):806~14
31 Lanier-Smith KL, Currie MG. Effect of glucocorticoids on the binding of atrial natriuretic peptide to endothelial cells. Eur J Pharmacol 1990;178(1):105~9
32 Kanda K, Ogawa K, Miyamoto N, Hatano T, Seo H, Matsui N. Potentiation of atrial natriuretic peptide-stimulated cyclic guanosine monophosphate formation by glucocorticoids in cultured rat renal cells. Br J Pharmacol 1989;96(4):795~800
33 Damjancic P, Vierhapper H. Permissive action of glucocorticoid substitution therapy on the effects of atrial natriuretic peptide (hANP) in patients with adrenocortical insufficiency. Exp Clin Endocrinol 1990;95(3):315~21
34 Radermacher J, Forstermann U, Frolich JC. Endothelium-derived relaxing factor influences renal vascular resistance. Am J Physiol 1990;259(1 Pt 2):F9~17
35 Tolins J, Shultz P, Raij L. Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. Hypertension 1991;17(6):909~916
36 Edwards RM. Effects of prostaglandins on vasoconstrictor action in isolated renal arterioles. Am J Physiol Renal Physiol 1985;248(6):F779~784
37 De Matteo R, May CN. Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep. Am J Physiol Regul Integr Comp Physiol 1999;276(4):R1125~1131
38 Bobadilla NA, Tapia E, Jimenez F, Sanchez-Lozada LG, Santamaria J, Monjardin A, et al. Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin. Am J Physiol Renal Physiol 1999;277(3):F464~471