Oxytocin and vasopressin constrict rat isolated uterine resistance arteries by activating vasopressin V1A receptors.

Both oxytocin and vasopressin cause potent and long-lasting vasoconstriction of uterine arteries from several species, including humans, and the resulting tissue ischemia is thought to be involved in the pathogenesis of primary dysmenorrhea. We have studied the effects of oxytocin and vasopressin in isolated resistance arteries (diameter, 90-120 microm) from non-pregnant rat uteri using two potent and selective receptor antagonists, SR 49059, a selective vasopressin V1A antagonist, and atosiban, a selective oxytocin antagonist. Uterine arteries with intact endothelium were mounted in a microvessel chamber, and pressurized to 75 mm Hg to allow the development of myogenic tone. Both vasopressin and oxytocin elicited a concentration-dependent vasoconstriction with a similar maximum effect (i.e., total vessel occlusion). The EC50 was 0.44 +/- 0.02 and 25 +/- 3.1 nM for vasopressin and oxytocin, respectively. Thus, vasopressin was 57-fold more potent than oxytocin. Schild analysis indicated that SR 49059 yielded a similar pA2 value against vasopressin-induced (pA2 = 8.96 +/- 0.60) or oxytocin-induced (pA2 = 9.06 +/- 0.23) contractions, suggesting that both agonists activated the vasopressin V1A receptor. In addition, atosiban (10(-7) M), a selective antagonist of the oxytocin receptor in the rat, did not antagonize the effect of vasopressin and oxytocin, showing that the oxytocin receptor is not involved in the response. In conclusion, these results suggest that V1A receptor stimulation is responsible for the vasoconstricting effects of both vasopressin and oxytocin in small diameter resistance arteries from the rat uterus.