Possible mechanisms for the suppressing action of 17beta-estradiol on beta-adrenoceptor-mediated vasorelaxation in rat aorta.
The mode of action of estrogen on beta-adrenoceptor-mediated relaxation was investigated by using isolated ring preparations of thoracic aorta from ovariectomized rats. Administration of 17beta-estradiol to ovariectomized rats significantly suppressed isoprenaline-induced relaxation of aortic rings. There was no alteration in the beta-adrenoceptor binding characteristics. The suppressing action of 17beta-estradiol on the N(G)-nitro-L-arginine and indomethacin-resistant relaxation induced by isoprenaline disappeared after pretreatment with N,N-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525A), an inhibitor of cytochrome P450 (CYP). The levels of CYP2C11 expression were the highest of the CYP mRNAs examined in rat aorta. 17beta-Estradiol replacement increased the expression of CYP2C11 mRNA in the aorta, compared with that in ovariectomized rats. These results suggest that estrogen suppresses beta-adrenoceptor-mediated vasorelaxation, and that the mechanisms may be associated with alterations in CYP2C11 metabolites.
Yamaguchi
K
K
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Honda
H
H
Tamura
K
K
Kogo
H
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001262:Atenolol / Q000494:pharmacology; D001667:Binding, Competitive; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D066298:In Vitro Techniques; D020120:Iodocyanopindolol / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010052:Ovariectomy; D011335:Proadifen / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011412:Propanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; C026777:ICI 118551; D004958:Estradiol; D001262:Atenolol; D020120:Iodocyanopindolol; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D007545:Isoproterenol; D009638:Norepinephrine