关键词: 内皮素, 降钙素基因相关肽, 脑血流, 心脏毒性, 激素

Abstract: 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.

Key words: endothelin, calcitonin gene-related peptide, cerebral blood flow, cardiac toxicity, hormone