Role of ET-1 in the regulation of coronary circulation.
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. ETB receptors 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 ETA receptor 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, ETB receptors 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.
Lavallée
Michel
M
Department of Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC H1T 1C8, Canada. lavallem@icm.umontreal.ca
Thorin
Eric
E
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D017466:Receptors, Endothelin; D019331:NG-Nitroarginine Methyl Ester