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 vasopressin of adrenoceptor‐mediated vasoconstriction was investigated in rat isolated perfused mesenteric arteries. 2 [Arg 8 ]vasopressin (1–10 n m ) dose‐dependently increased the perfusion pressure and enhanced the pressor response to the adrenoceptor agonist methoxamine (40 nmol) or electrical stimulation of periarterial nerves (16 Hz), at the concentration of 10 n m of [Arg 8 ]vasopressin up to 4 and 3 fold, respectively. 3 During prolonged exposure (45 min) the direct vasoconstrictor effect of [Arg 8 ]vasopressin (10 n m ) rapidly declined whereas the potentiation of methoxamine‐induced vasoconstriction was maintained. 4 The selective vasopressin V 1A receptor antagonist SR 49,059 (1–3 n m ) and the non‐selective V 1A/B and oxytocin receptor antagonist [deamino‐Pen 1 ,Tyr(Me) 2 ,Arg 8 ]vasopressin (15–45 n m ) inhibited the direct vasoconstrictor action of [Arg 8 ]vasopressin but had no effect on the enhancement of the pressor response to methoxamine or electrical stimulation. 5 The V 1B receptor agonist [deamino‐Cys 1 ,β‐(3‐pyridyl)‐D‐Ala 2 ,Arg 8 ]vasopressin (100–1000 n m ) and the V 2 receptor agonist [deamino‐Cys 1 ,D‐Arg 8 ]vasopressin (1–10 n m ) were devoid of any pressor activity and did not potentiate methoxamine‐evoked vasoconstriction. In contrast, [1‐triglycyl,Lys 8 ]vasopressin (100–1000 n m ) potentiated the methoxamine responses without per se inducing vasoconstriction. 6 In arteries precontracted with methoxamine (7.5 μ m ) pressor responses to [Arg 8 ]vasopressin (3–10 n m ) were not inhibited by a dose of SR 49,059 (3 n m ) 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 enhancement of adrenoceptor‐mediated pressor responses is insensitive to V 1A , V 1B , and oxytocin receptor antagonists and is not mimicked by selective agonists of V 1B and V 2 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.British Journal of Pharmacology (1998) 125 , 1120–1127; doi: 10.1038/sj.bjp.0702167