先天性心脏病患者血浆一氧化氮及其相关血管舒张因子水平与肺动脉压力关系的研究
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摘要
目的 通过测定左向右分流的先天性心脏病（CHD）患
者血浆一氧化氮（NO）及其介导的血管舒张因子如肾上
腺髓质素（ADM）、前列环素（PGI_2）、血管活性肠肽（VIP）、
心钠素（ANP）水平和肺动脉压力，探讨其在肺动脉高压
发生和发展中的意义。方法 选取行心内直视手术的CHD
患者40例为受试对象，根据心脏B超测定的肺动脉收缩
压水平，分为肺动脉高压组（PH组）25例和对照组15
例。应用单一试剂比色法测定血浆NO含量，放射免疫分
析法测定血浆ADM、ANP、PGI_2和VIP含量。结果 ①血
浆NO和ADM、PGI_2、VIP、ANP含量在PH组中都明显高
于对照组，P分别小于0.01、0.01、0.05、0.01和0.01。
②NO、ADM、PGI_2、VIP和ANP血浆浓度均与肺动脉收缩
压呈正相关，r值分别为0.54、0.50、0.64、0.49和0.81，
P分别小于0.01、0.01、0.01、0.05和0.01。③ADM、
PGI_2、VIP和ANP血浆浓度均与NO血浆浓度呈正相关，r
值分别为0.45、0.49、0.39和0.41，P分别小于0.05、
0.01、0.05和0.05。结论：①左向右分流的CHD患者NO
及其介导的血管舒张因子血浆水平随肺动脉压力升高而
升高。②ADM、PGI_2、VIP和ANP在提高NO血浆浓度方面，
即无协同作用，又无相加作用，可能存在NO的逃逸现象。
③NO及其介导的血管舒张因子的增高可能在延缓CHD肺
动脉高压的形成和发展中起重要作用。④NO及其介导的
血管舒张因子可用来估计CHD患者肺动脉高压的严重程
度，可能是判断CHD患者预后的重要指标。
Abstract
Objective: To study the significant role of the Nitric oxide
(NO) and its mediated vasodilator factors such as
adrenomedullin (ADM)~ prostacyclin (PGI2) vasoactive
intestinal peptide (VIP) and atrial natriuretic peptide (ANP)
in pulmonary hypertension and their relationships to
pulmonary pressure ,we assayed the plasma levels of NO.
ADM~. PGI2 VIP and ANP in congenital heart disease
patients (CUD) complicated by pulmonary hypertension and
control subjects. Methods: 40 patients with congenital
heart disease who would go through surgical treatment
were included. According the results of cardiac ultrasound,
the subjects were deviled pulmonary hypertension group(PH
group, 15 patients)and control group(25 patients). Plasma
levels of NO were measured by colorimetric assay. Plasma
levels of ADM~ PGI2~ VIP and ANP were measured by
specific radioimmunoassay. Results:OThe plasma levels of
NO and ADM~. PGI2~ VITh ANP in PH subjects increased
significantly in PH subjects than in control subjects, the
numbers P are respectively lower than 0.01 ~0.01~ 0.05~ 0.01
and 0.01. 甌he plasma levels of NO, as well as plasma
levels of ADM PGI2 VIP and ANP, were notably with
*relation to pulmonary arterial systolic pressure, the numbers
r were 0.54~ 0.50~ 0.640.49and 0.81 0.01 ~ 0.01 ~. 0.01~ 0.05
and 0.01. 甈lasma levels of ADM~ PGb~. VIP and AN
were correlated with plasma levels of NO , the numbers r
5
were 0.45~. 0.49~ 0.39 and 0.41 respectively ,the numbers P
were respectively lower than 0.05~ 0.01 ~ 0.05 and 0.05.
Conclusion: 0 The plasma levels of NO and its mediated
vasodilator factors in CHiD complicated by pulmonary
hypertension were increased with the raise of pulmonary
pressure. @~There are no cooperative roles and added roles
in increasing the plasma levels NO by NO and its mediated
vasodilator factors .The escape of NO may be exsisted. 0
The increasment of NO and its mediated vasodilator factors
play an important role in delaying of the genesis and
development in Cl-ID complicated by pulmonary
hypertension. ㏄lasma NO and its mediated vasodilator
factors can reflect the seriousness of pulmonary pressure in
patients with congenital heart disease . Therefore, plasma
Plasma NO and its mediated vasodilator factors may be very
important parameters for the prejudges of patients with
congenital heart disease.
者血浆一氧化氮（NO）及其介导的血管舒张因子如肾上
腺髓质素（ADM）、前列环素（PGI_2）、血管活性肠肽（VIP）、
心钠素（ANP）水平和肺动脉压力，探讨其在肺动脉高压
发生和发展中的意义。方法 选取行心内直视手术的CHD
患者40例为受试对象，根据心脏B超测定的肺动脉收缩
压水平，分为肺动脉高压组（PH组）25例和对照组15
例。应用单一试剂比色法测定血浆NO含量，放射免疫分
析法测定血浆ADM、ANP、PGI_2和VIP含量。结果 ①血
浆NO和ADM、PGI_2、VIP、ANP含量在PH组中都明显高
于对照组，P分别小于0.01、0.01、0.05、0.01和0.01。
②NO、ADM、PGI_2、VIP和ANP血浆浓度均与肺动脉收缩
压呈正相关，r值分别为0.54、0.50、0.64、0.49和0.81，
P分别小于0.01、0.01、0.01、0.05和0.01。③ADM、
PGI_2、VIP和ANP血浆浓度均与NO血浆浓度呈正相关，r
值分别为0.45、0.49、0.39和0.41，P分别小于0.05、
0.01、0.05和0.05。结论：①左向右分流的CHD患者NO
及其介导的血管舒张因子血浆水平随肺动脉压力升高而
升高。②ADM、PGI_2、VIP和ANP在提高NO血浆浓度方面，
即无协同作用，又无相加作用，可能存在NO的逃逸现象。
③NO及其介导的血管舒张因子的增高可能在延缓CHD肺
动脉高压的形成和发展中起重要作用。④NO及其介导的
血管舒张因子可用来估计CHD患者肺动脉高压的严重程
度，可能是判断CHD患者预后的重要指标。
Abstract
Objective: To study the significant role of the Nitric oxide
(NO) and its mediated vasodilator factors such as
adrenomedullin (ADM)~ prostacyclin (PGI2) vasoactive
intestinal peptide (VIP) and atrial natriuretic peptide (ANP)
in pulmonary hypertension and their relationships to
pulmonary pressure ,we assayed the plasma levels of NO.
ADM~. PGI2 VIP and ANP in congenital heart disease
patients (CUD) complicated by pulmonary hypertension and
control subjects. Methods: 40 patients with congenital
heart disease who would go through surgical treatment
were included. According the results of cardiac ultrasound,
the subjects were deviled pulmonary hypertension group(PH
group, 15 patients)and control group(25 patients). Plasma
levels of NO were measured by colorimetric assay. Plasma
levels of ADM~ PGI2~ VIP and ANP were measured by
specific radioimmunoassay. Results:OThe plasma levels of
NO and ADM~. PGI2~ VITh ANP in PH subjects increased
significantly in PH subjects than in control subjects, the
numbers P are respectively lower than 0.01 ~0.01~ 0.05~ 0.01
and 0.01. 甌he plasma levels of NO, as well as plasma
levels of ADM PGI2 VIP and ANP, were notably with
*relation to pulmonary arterial systolic pressure, the numbers
r were 0.54~ 0.50~ 0.640.49and 0.81 0.01 ~ 0.01 ~. 0.01~ 0.05
and 0.01. 甈lasma levels of ADM~ PGb~. VIP and AN
were correlated with plasma levels of NO , the numbers r
5
were 0.45~. 0.49~ 0.39 and 0.41 respectively ,the numbers P
were respectively lower than 0.05~ 0.01 ~ 0.05 and 0.05.
Conclusion: 0 The plasma levels of NO and its mediated
vasodilator factors in CHiD complicated by pulmonary
hypertension were increased with the raise of pulmonary
pressure. @~There are no cooperative roles and added roles
in increasing the plasma levels NO by NO and its mediated
vasodilator factors .The escape of NO may be exsisted. 0
The increasment of NO and its mediated vasodilator factors
play an important role in delaying of the genesis and
development in Cl-ID complicated by pulmonary
hypertension. ㏄lasma NO and its mediated vasodilator
factors can reflect the seriousness of pulmonary pressure in
patients with congenital heart disease . Therefore, plasma
Plasma NO and its mediated vasodilator factors may be very
important parameters for the prejudges of patients with
congenital heart disease.
引文
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2．何瑞英主编。心血管生理学。第一版。北京：人民卫生出版社 1987：203-211
3. Vane JR, et al.Regulatory functions of the vascular endothelium. New Engl J Med. 1967;59(8): 268-274
4．杜军保主编。缺氧性肺动脉高压。第一版。北京：北京医科大学、中国协和医科大学联合出版社 1994：35-49
5. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetycholine. Nature, 1980,288:373-378
6. Palmer RMJ,Ferrige AG,Moncada S et al. Nitric oxide release accounts for the biological activity of endothelium derived rekaxuibg factor. Nature, 1987, 327: 524-529.
7. Loke KE, Sobey CG, Dusting GJ et al. Cholinergic neurogenic vasodilation is mediated by nitric oxide in the dog hindlimb. Cardivoasc Res, 1994,28:542-546
8. Imai T, Kanno K et al. Inductin of nitric oxide synthase by cyclic AMP in rat VSMCs. J Hypertentension, 1994, 12(Suppl 3): S28-29
9. Buga GMM,Griscavage JM, Rogers NE et al. Negative feedback regulation of endothelial cell function by nitric oxide. Circ Res, 1993, 84(Suppl): 1-3
10．陈修 陈维周 曾贵云 等．心血管药理学，第二版 北京：人民卫生出版社 1997：124-130
11. Scott-Brden Ohyanagi-M; Nishigaki-K et al. Interaction between microvascular alpha 1-and alpha 2-adrenoceptors and endothelium-derived relaxing factor. Circ-Res. 1992 Jul; 71(1): 188-200
12. Custafsson L et al. Biochem Biophys Res Commun, 1991; 181:85-92
13． Calver A,Collier J,Vallance P,et al. Nitric oxide and cardiovascular control. Exp Physiol, 1993,78:303-308
14． Roberts JD, Chen TY, Kawai N, et al. Inhaled nitric oxide reverses pulmonary vasoxonstriction in the hypoxic and acidotic newborn lamb. Circ Res, 1993,72:246-251
15． Castillo L , Rojas T , Chapman T et al. Nitric oxide synthesis is decreased in persistent pulmonary hypertension of the newborn. Pediatr Res, 1993,33: 20A-24A
16． Giaid A, Saleh D.Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension.N Engl J Med,1995,333:214-221．
17． Dinh AT,Higenbottam TW,Clell CA, et al.Impairment of endothelium-dependent pulmonary artery relaxation in chronic obstructive lung disease.N Engl J Med, 1991, 324: 1539-1547
18． Takaya J, Teraguhi M, et al. Relation between plasma nitrate and mean pulmonary arteriral pressure in ventricular septal defect. Arch Dis C hildc 1998; 79 (6) : 498-501
19． Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT , et al . Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension . Lancet, 1991,338:1173
20． Kitamura K,Sakata J,Dangawa K,et al: Cloning and chara-ctarization of Cdna a precursor for human AM. Biochem Biophys Res Commun. 1993; 194: 720-725．
21． Sakata j,ShimOkubo T,Kitamura K,et al. Molecular cloning and biological activities of rat adrenomedullin,a hypotensive peptide.Biophys Res Commun. 1993; 195, 921-927．
22． Nishikimi T,Kitamura K,Saito Y,et al.Clinical strdies for the site of production and clearance of circulation adrenomedullin in human subjects Hypertension. 1994; 24: 600-604．
23． Ishimitsu Tet al.Biochem Biohys Res Commun, 1994;
203(1): 631-639
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2．何瑞英主编。心血管生理学。第一版。北京：人民卫生出版社 1987：203-211
3. Vane JR, et al.Regulatory functions of the vascular endothelium. New Engl J Med. 1967;59(8): 268-274
4．杜军保主编。缺氧性肺动脉高压。第一版。北京：北京医科大学、中国协和医科大学联合出版社 1994：35-49
5. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetycholine. Nature, 1980,288:373-378
6. Palmer RMJ,Ferrige AG,Moncada S et al. Nitric oxide release accounts for the biological activity of endothelium derived rekaxuibg factor. Nature, 1987, 327: 524-529.
7. Loke KE, Sobey CG, Dusting GJ et al. Cholinergic neurogenic vasodilation is mediated by nitric oxide in the dog hindlimb. Cardivoasc Res, 1994,28:542-546
8. Imai T, Kanno K et al. Inductin of nitric oxide synthase by cyclic AMP in rat VSMCs. J Hypertentension, 1994, 12(Suppl 3): S28-29
9. Buga GMM,Griscavage JM, Rogers NE et al. Negative feedback regulation of endothelial cell function by nitric oxide. Circ Res, 1993, 84(Suppl): 1-3
10．陈修 陈维周 曾贵云 等．心血管药理学，第二版 北京：人民卫生出版社 1997：124-130
11. Scott-Brden Ohyanagi-M; Nishigaki-K et al. Interaction between microvascular alpha 1-and alpha 2-adrenoceptors and endothelium-derived relaxing factor. Circ-Res. 1992 Jul; 71(1): 188-200
12. Custafsson L et al. Biochem Biophys Res Commun, 1991; 181:85-92
13． Calver A,Collier J,Vallance P,et al. Nitric oxide and cardiovascular control. Exp Physiol, 1993,78:303-308
14． Roberts JD, Chen TY, Kawai N, et al. Inhaled nitric oxide reverses pulmonary vasoxonstriction in the hypoxic and acidotic newborn lamb. Circ Res, 1993,72:246-251
15． Castillo L , Rojas T , Chapman T et al. Nitric oxide synthesis is decreased in persistent pulmonary hypertension of the newborn. Pediatr Res, 1993,33: 20A-24A
16． Giaid A, Saleh D.Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension.N Engl J Med,1995,333:214-221．
17． Dinh AT,Higenbottam TW,Clell CA, et al.Impairment of endothelium-dependent pulmonary artery relaxation in chronic obstructive lung disease.N Engl J Med, 1991, 324: 1539-1547
18． Takaya J, Teraguhi M, et al. Relation between plasma nitrate and mean pulmonary arteriral pressure in ventricular septal defect. Arch Dis C hildc 1998; 79 (6) : 498-501
19． Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT , et al . Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension . Lancet, 1991,338:1173
20． Kitamura K,Sakata J,Dangawa K,et al: Cloning and chara-ctarization of Cdna a precursor for human AM. Biochem Biophys Res Commun. 1993; 194: 720-725．
21． Sakata j,ShimOkubo T,Kitamura K,et al. Molecular cloning and biological activities of rat adrenomedullin,a hypotensive peptide.Biophys Res Commun. 1993; 195, 921-927．
22． Nishikimi T,Kitamura K,Saito Y,et al.Clinical strdies for the site of production and clearance of circulation adrenomedullin in human subjects Hypertension. 1994; 24: 600-604．
23． Ishimitsu Tet al.Biochem Biohys Res Commun, 1994;
203(1): 631-639
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25. Martinez-A; Miller-MJ; Unsworth-EJ; et al. Expression of adrenomedullin in normal human lung and in pulmonary tumors. Endocrinology. 1995 Sep; 136(9): 4099-4105
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