Endothelin receptor subtypes in resistance arteries from humans and rats.
OBJECTIVE
Endothelins bind to different receptor subtypes identified as ETA and ETB receptors, ETA receptors are present on smooth muscle cells of blood vessels. ETB receptors seem to predominate on endothelial cells of blood vessels, but may also be present on smooth muscle in some vascular beds. The aim of this study was to investigate the distribution of ETA and ETB receptors in human and in rat resistance arteries.


METHODS
Contractile responses to endothelin-1 and to the ETB agonist sarafotoxin S6c were investigated in human subcutaneous resistance arteries and in rat mesenteric resistance arteries mounted on a wire myograph.


RESULTS
Contractile responses to endothelin-1 were significantly reduced by the ETA selective antagonists BQ123 or BQ610 in human resistance arteries, and were almost abolished by the antagonists in rat arteries. The ETB agonist sarafotoxin S6c induced smaller responses than endothelin-1. When responses to sarafotoxin S6c were obtained in the presence of BQ610, the relatively small contractile response remained. It was slightly enhanced if the responses were obtained in the presence of the nitric oxide synthase inhibitor L-NAME or after removal of the endothelium.


CONCLUSIONS
Vasoconstrictor ETB receptors appear to be present in resistance vessels isolated from subcutaneous fat in humans and from the mesentery in rats, but their contribution to endothelin mediated constriction is small, particularly in rat resistance arteries. ETA receptors appear to be the more important endothelin receptor subtype in the human and rat resistance arteries examined.
Deng
L Y
LY
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Quebec, Canada.
Li
J S
JS
Schiffrin
E L
EL
D000273:Adipose Tissue / Q000098:blood supply*; D000328:Adult; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D014655:Vascular Resistance; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C087220:BQ 610; D001120:Arginine; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester