Vascular effects of [Arg8]vasopressin in the isolated perfused rat kidney.
The renal vascular effects of [Arg8]vasopressin (vasopressin) were investigated in the isolated perfused rat kidney. Vasopressin (0.01-3 nM) elicited a dose-dependent vasoconstriction in kidneys from Sprague Dawley rats, with a EC50 value of 0.206 +/- 0.044 nM. Inhibition of nitric oxide synthase by N omega-nitro-L-arginine (100 microM) shifted the vasopressin-induced vasoconstrictor response curve to the left. Inhibition of cyclooxygenase by indomethacin (10 or 30 microM) blunted the constriction induced by low concentrations of the peptide. Vasopressin, like angiotensin II but not noradrenaline, induced tachyphylaxis, SR 49059 ((2S)1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene- sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2- carboxamide) (1-30 nM), a new potent and selective non-peptide vasopressin V1A receptor antagonist, shifted the concentration-response curve for vasopressin to the right without decreasing the maximum contraction. Antagonism became competitive with a pA2 value (+/- S.D.) of 9.72 +/- 0.20 during inhibition of nitric oxide release. [Mpa1,D-Arg8]Vasopressin (desmopressin; 0.1-100 nM), or vasopressin (0.01-1 nM) after blockade of the vasopressin V1A receptor by SR 49059, induced no vasopressin V2 receptor-related renal relaxation in kidneys with vascular tone previously restored by noradrenaline or prostaglandin F2 alpha. These findings indicate that in the isolated perfused rat kidney vasopressin is a potent renal vasoconstrictor. The constriction depends on activation of smooth muscle vasopressin V1A receptors and is modulated by endothelial nitric oxide but not by prostacyclin or vasopressin V2 receptor-related vasodilation.
Barthelmebs
M
M
Institut de Pharmacologie (ERS 109 CNRS), Faculté de Médecine, Strasbourg, France.
Krieger
J P
JP
Grima
M
M
Nisato
D
D
Imbs
J L
JL
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011453:Prostaglandins / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology; D012076:Renal Agents / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D007211:Indoles; D011453:Prostaglandins; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; D012076:Renal Agents; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D009569:Nitric Oxide; C082134:relcovaptan; D009638:Norepinephrine