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 reported, little is known about whether pregnancy affects the responsiveness of this artery to oxytocin. If it does, is it a consequence of changed endothelial function, as has been proposed for some other vasoconstrictors. Furthermore, the receptor subtypes involved in oxytocin action on uterine artery has not been yet determined. Therefore the purposes of this study were to (1) determine the receptor subtypes involved in oxytocin action in non-pregnant and pregnant guinea-pig uterine artery and to (2) determine whether possible changes in uterine artery sensitivity to oxytocin during pregnancy are due to altered endothelial function. Therefore, the effect of oxytocin on non-pregnant and pregnant guinea-pig uterine arterial rings with and without endothelium was investigated. In non-pregnant guinea-pig uterine artery oxytocin induced contraction (pEC50 = 7.63) with greater potency than in pregnant guinea-pig uterine artery (pEC50 = 7.17). Removal of the endothelium did not affect oxytocin-induced contractions, regardless of the pregnancy status. The uterine arteries did not respond to [Thr4, Gly7]oxytocin. In the preparations studied, [d(CH2)5Tyr(Me)2]vasopressin and [d(CH2)5, D-Ile2, Ile4]vasopressin antagonized oxytocin action with the following pKB values ([d(CH2)5Tyr(Me)2]vasopressin versus [d(CH2)5, D-Ile2, Ile4]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 V1A receptors. The potency of oxytocin in uterine artery is decreased during pregnancy and this is not associated with altered endothelial function.
Jovanović
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Department of Clinical Pharmacology, Pharmacology and Toxicology, School of Medicine, Belgrade, Yugoslavia.
Jovanović
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S
Grbović
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D000818:Animals; D001158:Arteries; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D018045:Receptors, Oxytocin / Q000187:drug effects* / Q000502:physiology; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects
D018045:Receptors, Oxytocin; D010121:Oxytocin