ENHANCED RESPONSES OF THE BASILAR ARTERY TO ACTIVATION OF ENDOTHELIN-B RECEPTORS IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

We tested the hypothesis that responses of the basilar artery to selec tive activation of endothelin-B receptors are altered during chronic h ypertension. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to a selective endothelin-B receptor a gonist, IRL 1620, in stroke-prone spontaneously hypertensive rats (SHR SP). Under control conditions, baseline basilar artery diameter was sm aller in SHRSP (196+/-8 mu m [mean+/-SEM]) than in normotensive Wistar -Kyoto rats (WKY) (245+/-9 mu m, P<.05). Topical application of IRL 16 20 (10(-8) mol/L) dilated the basilar artery by 27+/-5% in WKY and 56/-4% in SHRSP (P<.05). Dilatation of the basilar artery in response to sodium nitroprusside was similar in WKY and SHRSP. In contrast, acety lcholine-induced vasodilatation in SHRSP was markedly impaired. N-G-Ni tro-L-arginine methyl ester and NG-nitro-L-arginine, inhibitors of nit ric oxide synthase, inhibited IRL 1620-induced vasodilatation in WKY. Neither N-G-nitro-L-arginine methyl ester nor indomethacin attenuated vasodilatation produced by IRL 1620 in SHRSP. The major finding is tha t dilator responses of the basilar artery to selective activation of e ndothelin-B receptors are paradoxically enhanced in SHRSP compared wit h WKY. Dilator responses of the basilar artery to endothelin-B recepto r activation are mediated by endothelium-derived relaxing factor in WK Y. In contrast, responses to activation of endothelin receptors in SHR SP do not depend on the production of nitric oxide or prostanoids.