Author:
Lavallée Michel,Thorin Eric
Abstract
Given that circulating ET levels in heart failure, in particular, may reach physiological threshold for coronary constrictor responses, the primary objective of the present review is to consider coronary vessels as an important target for circulating and locally produced endothelin(s). In healthy vessels, ET-1 causes biphasic coronary responses characterized by a transient dilation of large and small arteries followed by a sustained constriction. ETBreceptors are pivotal in the early dilation of resistance vessels, whereas dilation of conductance vessels may be a secondary phenomenon triggered by flow increases. Exogenous ET-1 causes coronary constriction almost exclusively through ETAreceptor activation. Human and canine large epicardial coronary vessels display significant baseline ET-1 dependent tone in vitro and in vivo, an ETA-dependent process. In contrast, ETBreceptors located on smooth muscle cells are apparently less important for producing constrictor responses. NO production may serve as an important counter-regulatory mechanism to limit ET-dependent effects on coronary vessels. Conversely, in a dysfunctional endothelium, the loss of NO may augment ET-1 production and activity. By lifting the ET-dependent burden from coronary vessels, ET receptor blockade should help to ensure a closer match between cardiac metabolic demand and coronary perfusion.Key words: endothelin, ET receptors, coronary vessels, coronary blood flow, nitric oxide, shear stress, atherosclerosis, humans, animals.
Publisher
Canadian Science Publishing
Subject
Physiology (medical),Pharmacology,General Medicine,Physiology
Cited by
16 articles.
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