Potentiation by endothelin-1 of vasoconstrictor response in stroke-prone spontaneously hypertensive rats.
Norepinephrine-induced vasoconstriction was significantly greater in perfused mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHRSPs) compared with cases of age-matched Wistar Kyoto rats (WKYs). Neither endothelin ET(A) receptor antagonist FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) nor endothelin ET(B) receptor antagonist BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-g-methylleucyl-D-1-methoxycarbonyl-tryptophanyl-D-norleucine] affected the increased responses observed in SHRSPs, suggesting that endogenous endothelin-1 is not involved in this phenomenon. Norepinephrine-induced vasoconstriction was significantly enhanced by subpressor dose of endothelin-1 (0.3 nM), both in SHRSPs and WKYs. In SHRSPs, endothelin-1-induced enhancement was abolished by FR139317, in contrast to the case with WKYs, in which BQ788 markedly suppressed endothelin-1-induced augmentation of norepinephrine responses. Our results indicate that exogenous endothelin-1 enhances contractile responses to norepinephrine in mesenteric arteries of WKYs and SHRSPs, through activation of different receptor subtypes.
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. matumrh@oysun01.oups.ac.jp
Y
Y
Matsumura
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S
Kita
T
T
Okui
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; C079574:FR 139317; C086539:BQ 788; D009638:Norepinephrine