Enhanced Responses of the Basilar Artery to Activation of Endothelin-B Receptors in Stroke-Prone Spontaneously Hypertensive Rats

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Abstract
Abstract We tested the hypothesis that responses of the basilar artery to selective activation of endothelin-B receptors are altered during chronic hypertension. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to a selective endothelin-B receptor agonist, IRL 1620, in stroke-prone spontaneously hypertensive rats (SHRSP). Under control conditions, baseline basilar artery diameter was smaller in SHRSP (196±8 μm [mean±SEM]) than in normotensive Wistar-Kyoto rats (WKY) (245±9 μm, P <.05). Topical application of IRL 1620 (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, acetylcholine-induced vasodilatation in SHRSP was markedly impaired. N G -Nitro- l -arginine methyl ester and N G -nitro- l -arginine, inhibitors of nitric 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 that dilator responses of the basilar artery to selective activation of endothelin-B receptors are paradoxically enhanced in SHRSP compared with WKY. Dilator responses of the basilar artery to endothelin-B receptor activation are mediated by endothelium-derived relaxing factor in WKY. In contrast, responses to activation of endothelin receptors in SHRSP do not depend on the production of nitric oxide or prostanoids.