Lack of effect of a selective vasopressin V(1A) receptor antagonist, SR 49,059, on potentiation by vasopressin of adrenoceptor-mediated presser responses in the rat mesenteric arterial bed

Abstract

1 The vasopressin receptor subtype involved in the enhancement by vasopressin of adrenoceptor-mediated vasoconstriction was investigated in rat isolated perfused mesenteric arteries. 2 [Arg8]vasopressin (1-10 nM) dose-dependently increased the perfusion pressure and enhanced the presser response to the adrenoceptor agonist methoxamine (40 nmol) or electrical stimulation of periarterial nerves (16 Hz), at the concentration of 10 nM of [Arg8]vasopressin up to 4 and 3 fold, respectively. 3 During prolonged exposure (45 min) the direct vasoconstrictor effect of [Arg8]vasopressin (10 nM) rapidly declined whereas the potentiation 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/B) and oxytocin receptor antagonist [deamino-Pen1,Tyr(Me)2,Arg8]vasopressin (15-45 nM ) inhibited the direct vasoconstrictor action of [Arg8]vasopressin but had no effect on the enhancement of the presser response to methoxamine or electrical stimulation. 5 The V(1B) receptor agonist [deamino-Cys1,β-(3-pyridyl)-D-Ala2,Arg8]vasopressin (100-1000 nM) and the V2 receptor agonist [deamino-Cys1,D-Arg8]vasopressin (1-10 nM) were devoid of any presser activity and did not potentiate methoxamine-evoked vasoconstriction. In contrast, [1-triglycyl,Lys8]vasopressin (100-1000 nM) potentiated the methoxamine responses without per se inducing vasoconstriction. 6 In arteries precontracted with methoxamine (7.5 μM) presser responses to [Arg8]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 [Arg8]vasopressin is mediated by V(1A) receptors while the enhancement of adrenoceptor-mediated presser responses is insensitive to V(1A), V(1B), and oxytocin receptor antagonists and is not mimicked by selective agonists of V(1B) and V2 receptors. In conclusion, an unusual interaction of vasopressin with V(1A) receptors, or even the existence of a novel receptor subtype, has to be considered.