Endothelin-1-induced circulatory response in the rat: the role of ETA and ETB receptors.
Production of the powerful vasoconstrictor endothelin-1 (ET1) is increased in a number of pathological conditions. This study was performed 1. to assess the effects of a twofold elevation of circulating ET1 on global hemodynamics and cardiac function, and 2. to determine the ET receptor subtypes that are responsible for this action. We have used the ETA receptor-selective antagonist BQ 610, the novel ETA receptor antagonist ETR-Pl/fl peptide and the specific ETB receptor antagonist IRL 1038 to investigate the role of these receptor subtypes in mediating circulatory changes induced by ET1 in anesthetized Wistar rats. ET1 infusion produced a significant rise in mean arterial pressure (MAP), elevated total peripheral resistance (TPR), and decreased cardiac output (CO). BQ 610 and ETR-Pl/fl pretreatment significantly attenuated the ET1-induced hemodynamic changes. Pretreatment with IRL 1038 had no effect on CO, but significantly reduced MAP and TPR elevation 20 min after ET1 infusion. These results suggest that ET1 may contribute to circulatory failure in conditions with increased ET1 production via a mechanism involving ETA receptors. ETB receptors, albeit to a lesser extent than ETA receptors, are also involved in mediating ET1-induced peripheral vasoconstriction in the rat.
Szalay
L
L
Department of Molecular Biology, Nagoya City University School of Medicine, Japan.
Boros
M
M
Baranyi
L
L
Okada
H
H
Nagy
S
S
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000145:classification* / Q000502:physiology; D012769:Shock / Q000209:etiology / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
C109027:ETR-p1-f1 antisense peptide; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; C087220:BQ 610; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21)