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

This study was conducted to evaluate the responsiveness of human nonpregnant myometrium to endothelin 1 (ET1) (10(-10) M-10(-6) M) and KCl (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 +/- 2 min, n=10, P<0.05) than in group 1 (20 +/- 2 min, 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 +/- 1.1 g x min, n=6, group 2: 11.9 +/- 1.6 g x 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 x min, n=6), as well as the basal tone (183.6 +/- 21%, n=6) compared with the two premenopausal groups. In all three groups KCl 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 KCl (80 mM) induced a similar pattern of contractility to that evoked by ET1 alone which, compared with KCl 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.