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  • Title: Potentiation by endothelin-1 of vasoconstrictor response in stroke-prone spontaneously hypertensive rats.
    Author: Matsumura Y, Kita S, Okui T.
    Journal: Eur J Pharmacol; 2001 Mar 09; 415(1):45-9. PubMed ID: 11245851.
    Abstract:
    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.
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