Vaxelaire J F, Laurent S, Briand V, Michel J B, Schmitt H
INSERM U 228, Paris.
Arch Mal Coeur Vaiss. 1988 Jun;81 Spec No:271-3.
The hypotensive effect of ANP has been associated with lowered cardiac output. Although only minor or no negative inotropic effect was found in vitro, a direct myocardial depressant effect of ANP remains a possible mechanism in vitro, in addition to the reduction in cardiac preload. Therefore we tested the hypothesis of a direct negative inotropic effect of ANP on the cultured chick embryo ventricular cell, an experimental system which contains no neural elements and no endogenous neurotransmitters. ANP (rat-ANP 1-23) 10(-8) M significantly and reversibly decreased contractility in spontaneously beating cells. A further decrease (-30 +/- 4 p. 100 of initial amplitude of contraction) was observed at 2.5 x 10(-7) M: -17 +/- 4 p. 100 of initial amplitude). The positive inotropic effect of angiotensin II (2.5 x 10(-7) M) on spontaneously beating cells was fully antagonized by ANP (2.5 x 10(-7) M) and amplitude of contraction decreased under control levels. By contrast (1) the increase in contractility in response to extra-cellular calcium (increased from 1.5 to 2.1 mM) was significantly less altered by ANP and (2) the time-course of the positive inotropic effect of the calcium-channel agonist BAY K 8644 (5 x 10(-9) M) or the beta-adrenergic agonist isoproterenol (10(-6) M) was unchanged by ANP. These results indicate a direct negative inotropic effect of ANP (1-23) on cultured chick heart cells and suggest an effect on intracellular messengers involved in the cardiac effects of angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
心钠素(ANP)的降压作用与心输出量降低有关。尽管在体外仅发现轻微或无负性肌力作用,但除了心脏前负荷降低外,ANP的直接心肌抑制作用在体外仍是一种可能的机制。因此,我们在培养的鸡胚心室细胞(一种不含神经成分和内源性神经递质的实验系统)上测试了ANP直接负性肌力作用的假说。10(-8) M的ANP(大鼠ANP 1 - 23)显著且可逆地降低了自发搏动细胞的收缩力。在2.5×10(-7) M时观察到进一步降低(降至初始收缩幅度的-30±4%):为初始幅度的-17±4%。血管紧张素II(2.5×10(-7) M)对自发搏动细胞的正性肌力作用被ANP(2.5×10(-7) M)完全拮抗,收缩幅度降至对照水平以下。相比之下,(1)细胞外钙增加(从1.5 mM增加到2.1 mM)引起的收缩力增加受ANP的影响显著较小,且(2)钙通道激动剂BAY K 8644(5×10(-9) M)或β-肾上腺素能激动剂异丙肾上腺素(10(-6) M)的正性肌力作用的时间进程不受ANP影响。这些结果表明ANP(1 - 23)对培养的鸡心脏细胞有直接负性肌力作用,并提示其对参与血管紧张素II心脏效应的细胞内信使有影响。(摘要截短于250字)