Prostaglandins are bioactive lipids and important mediators of uterine relaxation as well as contraction during pregnancy and labour. E series prostaglandins may directly contract or relax myometrium in a dose-dependent manner, with the relaxatory effects mediated through the prostanoid receptors EP(2) and EP(4). The aim of this study was to evaluate the pharmacological effects of prostaglandin analogues on isolated pregnant rat uterine contractility, at 10(-15) to 10(-9) M concentrations. Uterine strips from rats at 19 days of gestation were set up in organ baths at 37 degrees C, bathed in Krebs buffer and gassed with 95% O(2)/5% CO(2). Spontaneous contractions were recorded via a force transducer. Concentration ranges of 10(-15)-10(-9) M of PGE(2), PGF(2alpha) and a range of prostaglandin analogues were applied non-cumulatively to the tissues. Spontaneous contractions were recorded for 12 min post dose. Amplitude, frequency, baseline tone and percent contractility over 10 min periods were analysed. PGE(2), butaprost, 9-keto fluprostenol, 11-keto fluprostenol, 9-keto fluprostenol isopropyl ester, AL8810 and 15(S)-15-methyl PGE(2) all caused a decrease in percent contractility (P<0.05). These agents, plus Delta(12)PGJ(2) and 9-deoxy-9-methylene-16,16-dimethyl PGE(2), also decreased frequency of contraction (P<0.05). Only PGE(2), PGF(2alpha) and 11-keto fluprostenol decreased baseline tone (P<0.05). The lower concentrations of prostaglandins used here mediated inhibition of spontaneous contractility of pregnant rat myometrium. Use of selective agonists suggested that the prostanoid receptors EP(2) and DP(2) are responsible for this relaxatory effect.
[Show abstract][Hide abstract] ABSTRACT: Oxytocin pretreatment of pregnant rat myometrium has been shown to reduce the contractions produced by further administration of oxytocin, as a function of the desensitization phenomenon. It is unclear whether this phenomenon affects the contractions produced by various prostaglandins that are used in the management of postpartum hemorrhage. The objective of this study was to investigate the contractile effects of various prostaglandins after oxytocin pretreatment and to compare their relative efficacies in vitro on pregnant rat myometrial strips. Myometrial samples from 29 pregnant Wistar rats at term were isolated and pretreated with oxytocin (10(-8) mol/L, experimental group) or physiological salt solution (control group) for 1 hour. They were then subjected to dose-response testing with oxytocin (n = 32), PGF2α (n = 16), dinoprostone (n = 14), alprostadil (n = 14), or misoprostol (n = 15) with cumulative increases in the organ bath concentrations from 10(-10) to 10(-5) mol/L. The contractile efficacies of various prostaglandins and oxytocin during the dose response were analyzed using mixed linear modeling and compared between the groups. There was no significant difference in the amplitude, frequency, motility index (amplitude × frequency), or area under the curve of all prostaglandins between the groups pretreated with oxytocin and the control group. However, there was a significant decrease in the frequency (P = .02) and motility index (P = .05) in the dose-response curves of oxytocin in the groups pretreated with oxytocin compared with the control groups. Overall, oxytocin produced superior contractions compared with all other prostaglandins, while dinoprostone and misoprostol produced the weakest contractions. The uterotonic effects of various prostaglandins are not affected by oxytocin desensitization; and despite desensitization, oxytocin provides superior contractions compared with the prostaglandins.
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