内皮素对心血管、局部脑血流及一些激素作用的影响

内皮素(endothelin,ET)是两年前才发现的一种强有力的缩血管物质。我们通过离体血管收缩试验观察到,猪内皮素(pET)对人和大鼠的多种血管都有强烈的收缩作用。这种作用较5-羟色胺、去甲肾上腺素、神经肽Y等多种缩血管物质明显而持久,给大鼠注射ET,血压明显升高。家兔实验表明,少至110pg的ET注入颈内动脉即可使脑血流量减少。11ng的ET可以使脑血流量减少80%。局部脑血流量减少的程度和ET剂量相关。给大鼠静脉内注射大剂量ET(3₂μg/kg),心电图显示心肌缺血、传导阻滞和心脏停搏,大鼠几分钟内死亡。ET的这种心脏毒性可被早期应用降钙素基因相关肽(CGRP)或硝普钠(SNP)所防止。表明ET的心脏毒性可能是通过引起冠状动脉强烈而持久的收缩所致。ET可使血浆醛固酮升高,但抑制下丘脑分泌加压素(AVP)。因此,ET是一个极为重要的血压和血流的调节因子。

Effects of Endothelin on Blood Vessels and Heart of Rats and Regional Cerebral Blood Flow in Rabbits

Endothelin(ET) is known as a most potent constrictor of blood vessel. The molecular structure of ET is similar to sarafotoxin S6b. In present study we examined the effects of ET on blood vessels and heart in rats in vitro and vivo and the effect of ET on regional cerebral blood flow (rCBF) in rabbits. Our results show that in vitro ET(10mol/L) strongly constricted all arteries we used including basal cerebral artery, coronary artery and femoral artery which were isolated from human. The effect of ET was more than 1000 times as strong as noradrenaline and serotonin and much stronger than CCK. The contractile effect of ET lasted more than 2 hours and the effect could be attenuated by CGRP and BNP. The administration of ET at a dose no less than 110pg through the internal carotid artery induced a decline of rCBF in rabbits, The effect was dose-dependent. The intravenous injection of ET(32μg/kg) elicited various ECG abnormalities from T wave change to ventricular arrest and a decline of blood pressure in rats. The cardiac-toxicity caused by ET could be prevented by the administration of CGRP (46μg) or Sodium Nitroprusside (1mg/kg). However, the cardiac-toxicity caused by isoadrenalin could not be prevented by CGRP, it indicated that the cardiac-toxisity of ET is a result of vasoconstriction of ET on coronary arteries. We also found that the intracerebroventricular injection of ET (5ng, 10μl) elevated plasma aldosterone in rats. In vitro, the perfusion experiment showed that ET inhibited vasopresin secretion from hypothalamus. We conclude that ET plays a most important role in regulation of blood pressure and blood flow.