Progesterone modulates estradiol actions: acute effects at physiological concentrations

The progestin element of hormone replacement therapy may reduce the cardiop rotective actions of the estrogen component. Only high concentrations (mu M ) of progesterone directly relaxed U46619 (9,11-dideoxy-9 alpha, 11 alpha-m ethanoepoxy prostaglandin F2 alpha)-pre-contracted porcine coronary artery rings. A low concentration of progesterone (1 nM), with no effects of its o wn, shifted the relaxation curves of bradykinin and calcium ionophore A2318 7 to the right while not affecting those of sodium nitroprusside and levcro makalim. The negative influence that 1 nM progesterone exerted on bradykini n- and A23187-mediated relaxation was diminished when 1 nM 17 beta-estradio l was concomitantly added to the bathing medium. Conversely, the potentiati ng actions of 1 nM 17 beta-estradiol on relaxations elicited by sodium nitr oprusside and levcromakalim were reduced following simultaneous treatment w ith the same concentrations of progesterone. These findings represent the f irst evidence for an acute in vitro vascular effect of progesterone at a ph ysiologically relevant concentration and concur with previous in vivo repor ts demonstrating that progesterone may diminish the beneficial effects of e strogens. (C) 1999 Elsevier Science B.V. All rights reserved.