CHARACTERIZATION OF OXYTOCIN ACTIONS IN GUINEA-PIG ISOLATED UTERINE ARTERY - THE EFFECT OF PREGNANCY

While the contractile effect of oxytocin on uterine artery has been re ported, little is known about whether pregnancy affects the responsive ness of this artery to oxytocin. If it does, is it a consequence of ch anged endothelial function, as has been proposed for some other vasoco nstrictors. Furthermore, the receptor subtypes involved in oxytocin ac tion on uterine artery has not been yet determined. Therefore the purp oses of this study were to (1) determine the receptor subtypes involve d in oxytocin action in non-pregnant and pregnant guinea-pig uterine a rtery and to (2) determine whether possible changes in uterine artery sensitivity to oxytocin during pregnancy are due to altered endothelia l function. Therefore, the effect of oxytocin on non-pregnant and preg nant guinea-pig uterine arterial rings with and without endothelium wa s investigated In non-pregnant guinea-pig uterine artery oxytocin indu ced contraction (pEC(50) = 7.63) with greater potency than in pregnant guinea-pig uterine artery (pEC(50) = 7.17). Removal of the endotheliu m did not affect oxytocin-induced contractions, regardless of the preg nancy status. The uterine arteries did not respond to [Thr(4),Gly(7)]o xytocin. In the preparations studied, [d(CH2)(5)Tyr(Me)(2)]vasopressin and [d(CH2)(5), D-IIe(2), Ile(4)]vasopressin antagonized oxytocin act ion with the following pK(B) values ([d(CH2)(5)Tyr(Me)(2)]vasopressin versus [d(CH2)(5), D-IIe(2), IIe(4)]vasopressin): 8.24 versus 7.29 and 8.11 versus 7.17 for non-pregnant guinea-pig uterine artery with and without endothelium, respectively; 8.39 versus 7.25 and 8.35 versus 7. 25 for pregnant guinea-pig uterine artery with and without endothelium , respectively. We suggest that, in uterine arteries, oxytocin induces contraction by activation of vasopressin V-1A receptors. The potency of oxytocin in uterine artery is decreased during pregnancy and this i s not associated with altered endothelial function. (C) 1998 Elsevier Science B.V.