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(Hypertension. 1995;25:490-494.)
© 1995 American Heart Association, Inc.

Articles

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

Takanari Kitazono; Donald D. Heistad; Frank M. Faraci

From the Departments of Internal Medicine and Pharmacology, Center on Aging and Cardiovascular Center, University of Iowa College of Medicine; and the Veterans Administration Medical Center, Iowa City.

Correspondence to Donald D. Heistad, MD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242.

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.

Key Words: arginine • cerebral arteries • acetylcholine • endothelium-derived relaxing factor • nitro compounds • rats, inbred SHR

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