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人C型利钠肽:对血管紧张素II血流动力学及内分泌反应的影响

Human C-type natriuretic peptide: effects on the haemodynamic and endocrine responses to angiotensin II.

作者信息

Cargill R I, Struthers A D, Lipworth B J

机构信息

Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland, United Kingdom.

出版信息

Cardiovasc Res. 1995 Jan;29(1):108-11.

PMID:7895227
Abstract

OBJECTIVE

The aim was to study the effects of high dose systemic human C-type natriuretic peptide (CNP) infusion in man on systemic and pulmonary haemodynamics and the renin-angiotensin system before and after infusion of angiotensin II.

METHODS

Eight normal male volunteers were studied on two separate occasions when, after the subjects had been rested to reach a baseline haemodynamic state (T0), infusions of either human CNP (10 pmol.kg-1.min-1) or placebo (5% dextrose) were begun. After 30 min (T30) on each study day, a concomitant infusion of angiotensin II (6 ng.kg-1.min-1) was started, and both infusions ran together for a further 30 min (until T60). Measurements of systemic and pulmonary haemodynamic variables and the activity of the renin-angiotensin system were made at baseline (T0), after 30 min of CNP or placebo (T30), and after angiotensin II (T60).

RESULTS

Infusion of CNP had no significant effects on systemic or pulmonary haemodynamics or on baseline renin-angiotensin system activity compared with placebo. Infusion of angiotensin II produced significant systemic and pulmonary pressor effects and also stimulated aldosterone secretion. There were, however, no significant differences between the changes induced by angiotensin II (expressed as the difference between T30 and T60) when CNP was infused compared with placebo: change in mean systemic arterial pressure with CNP 26.6(SEM 2.3) mm Hg v placebo 30.3(3.6) mm Hg; change in mean pulmonary artery pressure with CNP 11.7(2.5) mm Hg v placebo 10.9(1.0) mm Hg; change in aldosterone concentration with CNP 219(40) pmol.litre-1 v placebo 242(40) pmol.litre-1.

CONCLUSIONS

At a dose of CNP which has previously been found to have marked haemodynamic effects in dogs, no effect on systemic or pulmonary haemodynamics was observed in man. Furthermore, CNP had no effect on the aldosterone or pressor responses to infused angiotensin II. The present study would suggest that CNP does not have a circulating endocrine role in cardiovascular homeostasis, although a paracrine role within vascular endothelium is perhaps more likely.

摘要

目的

本研究旨在探讨静脉输注大剂量人C型利钠肽(CNP)对人体在输注血管紧张素II前后的全身及肺血流动力学以及肾素-血管紧张素系统的影响。

方法

选取8名正常男性志愿者,在两个不同的时间段进行研究。在受试者休息至达到基础血流动力学状态(T0)后,分别开始输注人CNP(10 pmol·kg-1·min-1)或安慰剂(5%葡萄糖)。在每个研究日的30分钟(T30)后,同时开始输注血管紧张素II(6 ng·kg-1·min-1),两种输注同时持续30分钟(直至T60)。在基线(T0)、输注CNP或安慰剂30分钟后(T30)以及输注血管紧张素II后(T60)测量全身和肺血流动力学变量以及肾素-血管紧张素系统的活性。

结果

与安慰剂相比,输注CNP对全身或肺血流动力学以及基线肾素-血管紧张素系统活性均无显著影响。输注血管紧张素II产生显著的全身和肺血管升压作用,并刺激醛固酮分泌。然而,与安慰剂相比,输注CNP时血管紧张素II引起的变化(以T30和T60之间的差异表示)无显著差异:输注CNP时平均全身动脉压变化为26.6(标准误2.3)mmHg,安慰剂为30.3(3.6)mmHg;输注CNP时平均肺动脉压变化为11.7(2.5)mmHg,安慰剂为10.9(1.0)mmHg;输注CNP时醛固酮浓度变化为219(40)pmol·升-1,安慰剂为242(40)pmol·升-1。

结论

在犬类中先前已发现具有显著血流动力学效应的CNP剂量,在人体中未观察到对全身或肺血流动力学有影响。此外,CNP对输注血管紧张素II引起的醛固酮或升压反应无影响。本研究表明,CNP在心血管稳态中不具有循环内分泌作用,尽管其在血管内皮内的旁分泌作用可能更大。

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