McNeill J Robert
Cardiovascular Risk Factor Reduction Unit and Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Can J Physiol Pharmacol. 2003 Jun;81(6):522-32. doi: 10.1139/y03-016.
This article reviews data at the in vivo whole animal and human level. The importance of both flow and pressure recordings and of the methods used to record these variables is emphasized. Exogenous administration of endothelin-1 evokes a transient depressor response mediated by endothelial endothelinB receptors, but the predominate effect of endothelin-1 is a sustained increase in blood pressure resulting from increases in total peripheral resistance. Resistance in the superior mesenteric, renal, and hindquarter vascular beds of animals and forearm resistance in humans is increased. Both endothelinA and, to a lesser extent, endothelinB receptors on vascular smooth muscle mediate the increases in resistance. Endothelin-1 evokes decreases in the precapillary/postcapillary resistance ratio, resulting in increased capillary pressure and net transcapillary filtration. Endothelin-1 evokes increases in mean circulatory filling pressure in animals and in constriction of the human dorsal hand vein. This venoconstrictor activity is mediated primarily through endothelinA and to a lesser extent endothelinB receptors. Endogenously generated endothelin contributes to the hemodynamic effects of angiotensin and vasopressin in certain animal models of hypertension. Antagonists of endothelin evoke modest hemodynamic changes in healthy humans and in some healthy animals, and they decrease vascular resistance dramatically in several salt-sensitive rat models of hypertension and also in some hypertensive human subjects. Thus, endogenously generated ET appears to play a modest role in the healthy organism, but it likely plays a major role in many pathophysiological states as described in companion articles in this issue.
本文综述了体内全动物和人体水平的数据。强调了血流和压力记录以及用于记录这些变量的方法的重要性。外源性给予内皮素-1会引发由内皮内皮素B受体介导的短暂降压反应，但内皮素-1的主要作用是由于总外周阻力增加导致血压持续升高。动物的肠系膜上动脉、肾和后肢血管床的阻力以及人体的前臂阻力增加。血管平滑肌上的内皮素A受体以及程度较轻的内皮素B受体介导了阻力的增加。内皮素-1会使毛细血管前/后阻力比值降低，导致毛细血管压力升高和跨毛细血管净滤过增加。内皮素-1会使动物的平均循环充盈压升高，并使人的手背静脉收缩。这种静脉收缩活动主要通过内皮素A受体介导，程度较轻的通过内皮素B受体介导。在某些高血压动物模型中，内源性产生的内皮素参与了血管紧张素和血管加压素的血流动力学效应。内皮素拮抗剂在健康人类和一些健康动物中引起适度的血流动力学变化，并且在几种盐敏感性高血压大鼠模型以及一些高血压人类受试者中显著降低血管阻力。因此，内源性产生的内皮素在健康机体中似乎起适度作用，但如本期相关文章所述，它可能在许多病理生理状态中起主要作用。
