LACK OF EFFECT OF A SELECTIVE VASOPRESSIN V-1A RECEPTOR ANTAGONIST, SR 49,059, ON POTENTIATION BY VASOPRESSIN OF ADRENOCEPTOR-MEDIATED PRESSOR-RESPONSES IN THE RAT MESENTERIC ARTERIAL BED

1 The vasopressin receptor subtype involved in the enhancement by vaso pressin of adrenoceptor-mediated vasoconstriction was investigated in rat isolated perfused mesenteric arteries. 2 [Arg(8)]vasopressin (1-10 nM) dose-dependently increased the perfusion pressure and enhanced th e presser response to the adrenoceptor agonist methoxamine (40 nnol) o r electrical stimulation of periarterial nerves (16 Hz), at the concen tration of 10 nM of [Arg(8)]vasopressin up to 4 and 3 fold, respective ly. 3 During prolonged exposure (45 min) the direct vasoconstrictor ef fect of [Arg(8)]vasopressin (10 nM) rapidly declined whereas the poten tiation of methoxamine-induced vasoconstriction was maintained. 4 The selective vasopressin V-1A receptor antagonist SR 49,059 (1-3 nM) and the non-selective V-1A,V-B and oxytocin receptor antagonist [deamino-P en(1),Tyr(Me)2,Arg(8)]vasopressin (15-45 nM) inhibited the direct vaso constrictor action of [Arg(8)]vasopressin but had no effect on the enh ancement of the presser response to methoxamine or electrical stimulat ion. 5 The V-1B receptor agonist [deamino-Cys(1),beta-(3-pyridyl)-D-Al a(2),Arg(8)] (100-1000 nM) and the V-2 receptor agonist [deamino-Cys(1 ),D-Arg(8)]vasopressin (1-10 nM) were devoid of any presser activity a nd did not potentiate methoxamine-evoked vasoconstriction. In contrast , [1-triglycyl, Lys(8)]vasopressin (100-1000 nM) potentiated the metho xamine responses without per se inducing vasoconstriction. 6 In arteri es precontracted with methoxamine(7.5 mu M) presser responses to [Arg( 8)]vasopressin (3-10 nM) were not inhibited by a dose of SR 49,059 (3 nM) which abolished the peptide's vasoconstrictor effect under control conditions. 7 These data show that the direct vasoconstrictor effect of [Arg(8)]vasopressin is mediated by V-1A receptors while the enhance ment of adrenoceptor-mediated presser responses is insensitive to V-1A , V-1B, and oxytocin receptor antagonists and is not mimicked by selec tive agonists of V-1B and V-2 receptors. In conclusion, an unusual int eraction of vasopressin with V-1A receptors, or even the existence of a novel receptor subtype, has to be considered.