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 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 microns [mean +/- SEM]) than in normotensive Wistar-Kyoto rats (WKY) (245 +/- 9 microns, 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. NG-Nitro-L-arginine methyl ester and NG-nitro-L-arginine, inhibitors of nitric oxide synthase, inhibited IRL 1620-induced vasodilatation in WKY. Neither NG-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.
Kitazono
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Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Heistad
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Faraci
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D010446:Peptide Fragments; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin