VASCULAR EFFECTS OF [ARG(8)]VASOPRESSIN IN THE ISOLATED-PERFUSED RAT-KIDNEY

The renal vascular effects of [Arg(8)]vasopressin (vasopressin) were i nvestigated in the isolated perfused rat kidney. Vasopressin (0.01-3 n M) elicited a dose-dependent vasoconstriction in kidneys from Sprague Dawley rats, with a EC(50) value of 0.206 +/- 0.044 nM. Inhibition of nitric oxide synthase by N-omega-nitro-L-arginine (100 mu M) shifted t he vasopressin-induced vasoconstrictor response curve to the left. Inh ibition of cyclooxygenase by indomethacin (10 or 30 mu M) blunted the constriction induced by low concentrations of the peptide. Vasopressin , like angiotensin II but not noradrenaline, induced tachyphylaxis. SR 49059 o-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide) (1-30 nM), a new potent and selective non-peptide vasopressin V-1A receptor antago nist, shifted the concentration-response curve for vasopressin to the right without decreasing the maximum contraction. Antagonism became co mpetitive with a pA(2) value (+/-S.D.) of 9.72 +/- 0.20 during inhibit ion of nitric oxide release. [Mpa(1),D-Arg(8)]Vasopressin (desmopressi n; 0.1-100 nM), or vasopressin (0.01-1 nM) after blockade of the vasop ressin V-1A receptor by SR 49059, induced no vasopressin V-2 receptor- related renal relaxation in kidneys with vascular tone previously rest ored by noradrenaline or prostaglandin F-2 alpha. These findings indic ate that in the isolated perfused rat kidney vasopressin is a potent r enal vasoconstrictor. The constriction depends on activation of smooth muscle vasopressin V-1A receptors and is modulated by endothelial nit ric oxide but not by prostacyclin or vasopressin V-2 receptor-related vasodilation.