INVESTIGATION OF THE NEGATIVE INOTROPIC EFFECTS OF 17-BETA-ESTRADIOL IN HUMAN ISOLATED MYOCARDIAL TISSUES

1 The aim of the present study was to evaluate the effects of 17 beta- oestradiol in human myocardium. The effects of 17 beta-oestradiol, pro gesterone and testosterone on force of contraction were investigated i n electrically driven isolated atrial trabeculae and ventricular papil lary muscles from human hearts in the presence and absence of Bay K 86 44, a calcium channel agonist. In addition, the effects of 17 beta-oes tradiol, progesterone and testosterone on binding of [H-3]-PN 200 110 were assessed in membranes prepared from human ventricular myocardium. 2 17 beta-Oestradiol elicited a negative inotropic effect in atrial I C50: 7.1 mu mol l(-1), confidence interval 3.8 to 13.4, n=3) and ventr icular preparations (IC50: 4.6 mu mol l(-1), confidence interval 2.2 t o 9.4, n=3) as compared with solvent controls. There was no significan t difference (P>0.05) of IC50 values in the absence and presence of is oprenaline (0.01 mu mol l(-1)) in atrial (IC50: 10.8 mu mol l(-1), con fidence interval 9.1 to 12.9, n=6) and ventricular preparations (IC50: 9.4 mu mol l(-1), confidence interval 7.3 to 11.9, n=8).3 17 beta-Oes tradiol at 30 mu mol l(-)1 induced a significant rightward shift of th e concentration-response curves for the positive inotropic effect of B ay K 8644 in atrial preparations (EC(50): 0.13 mu mol l(-1), confidenc e interval 0.08 to 0.19, n=6; EC(50) with 17 beta-oestradiol: 0.58 mu mol l(-1), confidence interval 0.33 to 0.83, n=6, P<0.05) and ventricu lar preparations (EC(50): 0.07 mu mol l(-1), confidence interval 0.04 to 0.11, n=8; EC(50) with 17 beta-oestradiol: 0.3 mu mol l(-1), confid ence interval 0.18 to 0.49, n=8, P<0.05). Testosterone, progesterone a t 30 mu mol l(-1) and the solvent control had no significant effect on the concentration-response curves to Bay K 8644. 4 In membranes prepa red from human ventricular myocardium the effect of 17 beta-oestradiol on binding of [H-3]-PN 200 110, an antagonist at the 1,4 dihydropyrid ine binding site, was not different from that observed with progestero ne, testosterone or solvent controls. 5 In myocardial membranes no spe cific oestrogen receptors were demonstrated by [H-3]-oestradiol bindin g studies. 6 Thus, the calcium antagonistic property of 17 beta-oestra diol cannot be attributed to a direct interaction with 1,4 dihydropyri dine binding sites.