CHARACTERIZATION OF RECEPTORS MEDIATING CONTRACTION OF THE RAT ISOLATED SMALL MESENTERIC-ARTERY AND AORTA TO ARGININE-VASOPRESSIN AND OXYTOCIN

1 The exact nature of the receptor subtype(s) involved in the action o f arg-vasopressin (AVP) on the rat aorta and small mesenteric artery ( SMA) is controversial. Therefore, we have studied the effects of the s elective V-1A receptor antagonists, OPC 21268 and SR 49059, and the ox ytocin (OT) receptor antagonist, atosiban, on the AVP- and CT-induced contractions of the two vessels. 2 AVP and OT displayed similar intrin sic activities in the rat aorta and SMA, but AVP was similar to 130 fo ld and similar to 500 fold more potent than OT, respectively. In the r at aorta, Hill slopes (n(H)) were similar for OT and AVP. However, in rat SMA, the OT concentration-effect (E/[A]) curve was significantly s teeper than the AVP E/[A] curve (n(H) = 3.3 +/- 0.20, 2.3 +/- 0.15; P < 0.001). 3 In the aorta OPC 21268, SR 49059 and atosiban competitivel y antagonized the AVP and OT E/[A] curves. Except for atosiban and SR 49059 against AVP, competitive antagonism was also observed in the SMA . Atosiban caused concentration-dependent steepening of the AVP E/[A] curve, whereas SR 49059 decreased the upper asymptote. 4 Schild analys is yielded affinities indicative of V-1A receptor involvement in both vessels: pK(B)/pA(2) = 9.20 - 9.48, 7.56 - 7.71 and 6.19 - 6.48 for SR 49059, OPC 21268 and atosiban, respectively. 5 Neither AVP nor OT rel axed U46619 pre-contracted aorta or SMA in the presence of SR 49059, s uggesting no interference of a vasodilatory component. 6 Despite predo minant involvement of V-1A receptors in both vessels, the different Hi ll slopes of AVP and OT E/[A] curves as well as the steepening of the AVP E/[A] curves by atosiban are indicative of receptor heterogeneity in the rat SMA.