Dilatation of the basilar artery in response to selective activation of endothelin B receptors in vivo.
The objective of this study was to examine effects of activation of endothelin (ET) B receptors on tone of the basilar artery in vivo. By using a cranial window in anesthetized rats, we examined the effects of IRL 1620, a selective ETB receptor agonist, on diameter of the basilar artery. Under control conditions, diameter of the basilar artery was 214 +/- 6 microns (mean +/- S.E.). Topical application of IRL 1620 (10(-8) mol/l) for 4 min dilated the basilar artery by 30 +/- 4%. Marked desensitization of vasodilator responses was observed in response to a second application of IRL 1620, but not acetylcholine, which indicates a homologous nature of desensitization. REA/001, an ETA/ETB receptor antagonist, abolished IRL 1620-induced dilatation of the basilar artery. BQ 123, a selective ETA receptor antagonist, inhibited constriction in response to ET-1, but did not affect dilator responses of the basilar artery to IRL 1620. Both NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine, inhibitors of nitric oxide synthase, produced marked inhibition of dilator responses of the basilar artery to IRL 1620 without inhibiting vasodilator responses to sodium nitroprusside. Indomethacin did not inhibit vasodilatation in response to IRL 1620. These findings suggest that activation of ETB receptors produces dilatation of the basilar artery in vivo. Dilator responses of the basilar artery to activation of ETB receptors are dependent on production of nitric oxide.
Kitazono
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Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA.
Heistad
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Faraci
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019335:Nitroarginine; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C074308:sovateltide; D019335:Nitroarginine; D001120:Arginine; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin