The role of oxytocin receptors and vasopressin V-1a receptors in uterine contractions in rats: Implications for tocolytic therapy with oxytocin antagonists

OBJECTIVE: The objective of the study was to determine in the rat model whether the uterotonic action of vasopressin is mediated by the vasopressin V-1a receptor in the uterus, by the oxytocin receptor, or by both. The purpose is to assess whether the anti-V-1a activity of oxytocin antagonists is a desirable pharmacologic property in tocolytic therapy for preterm labor. STUDY DESIGN: Dose-response characteristics of the uterotonic action of oxytocin and arginine vasopressin were compared and analyzed by the in vitro cumulative dose-response curve technique. A nonselective oxytocin-V-1a receptor antagonist, a selective oxytocin receptor antagonist, and a selective V-1a receptor antagonist were selected for this study. Their relative effectiveness in inhibiting the uterine contractile responses induced by oxytocin and by arginine vasopressin in the isolated rat uterus was examined. RESULTS: The uterotonic dose-response curves for oxytocin and arginine vasopressin were parallel and had the same maximal response. The nonselective oxytocin/V-1a receptor antagonist and the selective oxytocin receptor antagonist were equally potent in inhibiting the uterine contractions induced by either oxytocin or arginine vasopressin, whereas the selective V-1a receptor antagonist had no antiuterotonic activity. Inhibition by the selective oxytocin antagonist caused a similar parallel shift to the right of the dose-response curves for oxytocin and arginine vasopressin. CONCLUSIONS: The parallel dose-response curves for oxytocin and arginine vasopressin suggest that the uterotonic action of vasopressin is also mediated by the oxytocin receptor. Arginine vasopressin binds to both oxytocin and V-1a receptors in the uterus, but the activation of V-1a receptors appears not to be a mechanism involved in the uterine-stimulating action of vasopressin. The anti-V-1a activity of oxytocin antagonists does not contribute to tocolytic efficacy and may represent an undesirable side effect. By blocking the vascular V-1a receptors, it may compromise the patient's ability to maintain arterial blood pressure during hemorrhage.