Contractile effects of prostaglandins, oxytocin, and endothelin-1 in human myometrium in vitro: Refractoriness of myometrial tissue of pregnant women to prostaglandins E₂ and F_2α

Whereas there is much evidence in support of a role for prostaglandins (PC) in the parturitional process, it has not been demonstrated unequivocally that PGs are the physiological uterotonins involved in the induction of the myometrial contractions of spontaneous labor in women. This study was conducted to evaluate the contractile responsiveness of human myometrial tissue in vitro to PGs and to compare this response with that of other uterotonins, viz. oxytocin and endothelin-1. We found that treatment of uterine smooth muscle strips obtained from nonpregnant and pregnant women with PGE₂ (10^-8-10^-6 M) caused a biphasic response characterized by an initial single contraction of increased amplitude and duration, followed by relaxation and a long period (10-15 min) of quiescence. Conversely, PGE₂ acted in rat myometrium to cause a monophasic response of increased contractile frequency and force. Whereas uterine smooth muscle from nonpregnant women was responsive to PGF_2α, the contractile responsiveness of myometrium from pregnant women was weak. This weak response to PGF_2α, was found in myometrium of women in labor and in myometrium of women not in labor. 15-Methyl-PGF_2α evoked a small response in myometrium from pregnant women. Under identical in vitro conditions, PGF_2α (10^-8-10^-6 M) and 15-methyl-POF_2α (10^-6 M) caused sustained contractions in human vascular smooth muscle tissues (fetal aorta and arterial smooth muscle from chorionic vessels). Similarly, oxytocin and endothelin-1 (in myometrium from pregnant women) were effective in stimulating the force and frequency of myometrial contraction in vitro. We conclude that the myometrium of pregnant women, as evaluated in vitro, is refractory to the contractile effects of PGE₂, and PGF_2α.