Endothelium- and cytochrome P-450-dependent relaxation induced by isoproterenol in rat aortic rings.
In rat aortic rings, the mechanism of endothelium-dependent relaxation induced by isoproterenol is examined. Pretreatment with (+/-)-1-[2,3]-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methyleth yl)amino] -2-butanol (ICI-118,551), a beta 2-adrenoceptor antagonist, or atenolol, a beta 1-adrenoceptor antagonist, partly inhibited the relaxing response to isoproterenol. The relaxing response to isoproterenol in the presence of ICI-118,551 or atenolol was markedly inhibited by removal of endothelium. In the aorta pretreated with ICI-118,551 or atenolol, residual relaxing response to isoproterenol was also inhibited by 2-methyl-1,2-di-3-pyridyl-1-propanone (metyrapone), alpha-naphthoflavone or 8-methoxypsoralen, cytochrome P-450 monoxygenase inhibitors, and methylene blue, but not by indomethacin, a cyclooxygenase inhibitor, 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1, 4-benzoquinone (AA861), a 5-lipoxygenase inhibitor, NG-nitro-L-arginine (NOARG), a nitric oxide synthase inhibitor, Zn protoporphyrin IX, a heme oxygenase inhibitor, or yohimbine, a alpha 2-adrenoceptor antagonist. In the aorta denuded of endothelium, metyrapone did not affect the residual relaxing response to isoproterenol in the presence of atenolol. These results suggest that the cytochrome P-450 system may be involved in the endothelium-dependent relaxation induced by isoproterenol through beta 1- and beta 2-adrenoceptor activation.
Satake
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N
Department of Pharmacology, University of Hawaii, School of Medicine, Honolulu 96822, USA.
Shibata
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M
Shibata
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S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D003577:Cytochrome P-450 Enzyme System; D007545:Isoproterenol