In vitro effects of endothelin-1 on the contractility of myometrium obtained from pre- and postmenopausal women

Abstract

This study was conducted to evaluate the responsiveness of human nonpregnant myometrium to endothelin 1 (ET1) (10-10 M-10-6 M) and KC1 (80 mM) in relation to the hormonal profile of the women, who were allocated into three groups: group 1, premenopausal follicular phase, n = 14, group 2, premenopausal luteal phase, n = 20, and group 3, postmenopausal women, n = 12. At a concentration of 10-6 M, ET1 in both groups 1 and 2 induced very low ripples of high frequency (group 1:80 ± 14%, n = 5, group 2:314 ± 63%, n = 11; P<0.05 compared with the pretreatment frequency) which lasted significantly longer in group 2 (29 ± 2min, n = 10, P<0.05) than in group 1 (20 ± 2min, n = 5), increasing the basal tone (group 1: 57.9 ± 6%, n = 5, group 2: 64.4 ± 4%, n = 6), the amplitude of myometrial contractility (group 1: 1.2 ± 0.07 g, n = 5, group 2:1.6 ± 0.1 g, n = 7, P<0.05) and the area under the contractility curve (AUC; group 1: 8.4 ± 1.1g × min, n = 6, group 2: 11.9 ± 1.6g × min, n = 11). In group 3, ET1 (10-6 M) created a sustained long-lasting contraction (initial phase: 43 ± 6 min, n = 6) characterized by the complete obliteration of spontaneous contractility with no ripples at all, and increasing significantly (P<0.05) the amplitude of myometrial contractility (2.8 ± 0.5 g, n = 6), the AUC (24.7 ± 3.3 g × min, n = 6), as well as the basal tone (183.6 ± 21%, n = 6) compared with the two premenopausal groups. In all three groups KC1 exposure induced an initial rise (mean amplitude value: 1.1 g) followed by a relaxation phase to the primal baseline level (mean duration value: 12 min). Addition of ET1 (10- 6 M) to KC1 (80 mM) induced a similar pattern of contractility to that evoked by ET1 alone which, compared with KC1 alone lasted significantly longer (P<0.05) in all three groups (group 1:20 ± 2 min, n = 6; group 2:23 ± 2 min, n = 6; group 3:35 ± 3 min, n = 5). In group 3, the percentage change in basal tone was significantly smaller following KCl than after the combination of KCl plus ET1 (149 ± 16%, n = 5; P<0.01), indicating a different mechanism of contractility between KCl and ET1. These results demonstrate for the first time differences in myometrial response to ET1 between pre- and postmenopausal women. It is suggested that KCl and ET1 affect uterine contractility through different mechanisms and that ovarian steroids may play a regulatory role in human uterine responsiveness to ET1.