Potentiation by endothelin-1 of vasoconstrictor response in stroke-prone spontaneously hypertensive rats

Norepinephrine-induced vasoconstriction was significantly greater in perfus ed mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHR SPs) compared with cases of age-matched Wistar Kyoto rats (WKYs). Neither e ndothelin ETA receptor antagonist FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahyd ro-1 H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1 H-indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) nor endothelin ETB receptor antagonist BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-methylleu cyl-D-1-methoxycarbonyl-tryptophanyl-D-norleucine] affected the increased r esponses observed in SHRSPs, suggesting that endogenous endothelin-1 is not involved in this phenomenon. Norepinephrine-induced vasoconstriction was s ignificantly enhanced by subpressor dose of endothelin-1 (0.3 nM). both in SHRSPs and WKYs. Ln SHRSPs, endothelin-1-induced enhancement was abolished by FR139317, in contrast to the case with WKYs, in which BQ788 markedly sup pressed 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 activ ation of different receptor subtypes. (C) 2001 Published by Elsevier Scienc e B.V.