Possible mechanisms for the suppressing action of 17 beta-estradiol on beta-adrenoceptor-mediated vasorelaxation in rat aorta

The mode of action of estrogen on P-adrenoceptor-mediated relaxation was in vestigated by using isolated ring preparations of thoracic aorta from ovari ectomized rats. Administration of 17 beta -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 17 beta -estradiol on the N-G-nitro-L-arginine an d indomethacin-resistant relaxation induced by isoprenaline disappeared aft er pretreatment with N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochlor ide (SKF 525A), an inhibitor of cytochrome P450 (CYP). The levels of CYP2C1 1 expression were the highest of the CYP mRNAs examined in rat aorta. 17 be ta -Estradiol replacement increased the expression of CYP2C11 mRNA in the a orta, compared with that in ovariectomized rats. These results suggest that estrogen suppresses beta -adrenoceptor-mediated vasorelaxation, and that t he mechanisms may be associated with alterations in CYP2C11 metabolites. (C ) 2001 Published by Elsevier Science B.V.