Oxytocin and vasopressin constrict rat isolated uterine resistance arteries by activating vasopressin V-1A receptors

Both oxytocin and vasopressin cause potent and long-lasting vasoconstrictio n of uterine arteries from severed species, including humans, and the resul ting tissue ischemia is thought to be involved in the pathogenesis of prima ry dysmenorrhea. We have studied the effects of oxytocin and vasopressin in isolated resistance arteries (diameter, 90-120 mu m) from non-pregnant rat uteri using two potent and selective receptor antagonists, SR 49059, a sel ective vasopressin V-1A antagonist, and atosiban, a selective oxytocin anta gonist. Uterine arteries with intact endothelium were mounted in a microves sel chamber, and pressurized to 75 mm Hg to allow the development of myogen ic tone. Both vasopressin and oxytocin elicited a concentration-dependent v asoconstriction 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 oxytoci n, respectively. Thus, vasopressin was 57-fold more potent than oxytocin. S child analysis indicated that SR 49059 yielded a similar pA(2) value agains t vasopressin-induced (pA(2) = 8.96 +/- 0.60) or oxytocin-induced (pA(2) = 9.06 +/- 0.23) contractions, suggesting that both agonists activated the va sopressin V-1A receptor. In addition, atosiban (10(-7) M), a selective anta gonist of the oxytocin receptor in the rat, did not antagonize the effect o f vasopressin and oxytocin, showing that the oxytocin receptor is not invol ved in the response. In conclusion, these results suggest that V-1A recepto r stimulation is responsible for the vasoconstricting effects of both vasop ressin and oxytocin in small diameter resistance arteries from the rat uter us. (C) 1999 Elsevier Science B.V. All rights reserved.