Cardiovascular responses mediated by two types of endothelin ET(B) receptor in spontaneously hypertensive and Wistar-Kyoto rats.
This study shows the effects of a selective endothelin ET(B) receptor agonist, IRL 1720 {Ac-[Ala11,15]endothelin-1-(8-21)}, on cardiovascular responses in anesthetized spontaneously hypertensive rats and Wistar-Kyoto rats. Single intravenous bolus injection of IRL 1720 caused a dose-related short-lasting fall in blood pressure, left ventricular pressure and myocardial contractility. However, repeated intravenous bolus injection of 10(-5) mol/kg IRL 1720 produced a biphasic response consisting of an initial short-lasting decrease followed by a sustained increase in these parameters. The initial decrease was reduced, whereas the following increase was enhanced with the repeated injections of IRL 1720. The cardiovascular pressor response was not inhibited by the endothelin ET(A) receptor antagonist, FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl] amino-4-+methylpentanoyl] amino-3-[3-(1-methyl-1H-indolyl)]propionyl]amino -3- (2-pyridyl)propionic acid). The effects of IRL 1720 were qualitatively similar but more potent in spontaneously hypertensive rats than in Wistar-Kyoto rats. These results suggest the existence of two types of endothelin ET(B) receptor for IRL 1720: a tachyphylactic endothelin ET(B) receptor that mediates cardiovascular depressor responses and a less tachyphylactic endothelin ET(B) receptor that mediates pressor responses in the rat.
Kuwahara
M
M
Department of Comparative Pathophysiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
Masuda
T
T
Tsubone
H
H
Sugano
S
S
Karaki
H
H
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects; D005268:Femoral Vein / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000819:agonists*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; C099076:IRL 1720; D007211:Indoles; D010446:Peptide Fragments; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C079574:FR 139317