Nitric oxide, but not vasopressin V₂ receptor-mediated vasodilation, modulates vasopressin-induced renal vasoconstriction in rats.

Loichot, Cécile; Cazaubon, Catherine; De Jong, Wybren; Heiwig, Jean-Jacques; Nisato, Dino; Imbs, Jean-Louis; Barthelmebs, Mariette

The renal vascular response to vasopressin and its modulation were evaluated in vivo by infusing the peptide directly into the renal artery of anaesthetized rats. The intra-renal artery (i.r.a) infusion of vasopressin induced a dose-dependent decrease in renal blood flow. Vasoconstriction was obvious at a dose of 3 ng/kg per min and reached a maximum at 100 ng/kg per min. The dose required for a half-maximal response (ED50) was 24±4 ng/kg per min (mean±SEM, n=8), corresponding to an estimated concentration in renal arterial blood required for a half-maximal response (EC50) of 1.9±0.6 nM. Thiobutabarbitone anaesthesia markedly increased plasma vasopressin concentration. This increase was prevented partially by hypotonic hydration of the rats without any change in the renal vascular response to exogenous vasopressin. Vasopressin-induced vasoconstriction dose/response curves were similar in homozygous and heterozygous Brattleboro rats. Infusion of desmopressin (1–1000 ng/kg per min, i.r.a.), a vasopressin V2 receptor-selective agonist, failed to induce renal vasodilation or vasoconstriction. In the presence of SR 49059 (1 mg/kg i.v.), a vasopressin V1A receptor antagonist that completely abolished the vasopressin-induced renal vasoconstriction, desmopressin again failed to induce vasodilation. Inhibition of nitric oxide synthase by Nω-nitro-l-arginine (L-NNA, 100 µg/kg for 10 min and 7.5 µg/kg per min, i.r.a.) enhanced vasopressin-induced renal vasoconstriction (EC50 0.6±0.1 nM, P2 receptor activation or prostanoid release. In contrast, NO release contributed to the attenuation of vasopressin-induced renal vasoconstriction.

RENAL artery; PEPTIDES; NITRIC oxide; VASODILATION; BLOOD circulation; AMINO acids

Naunyn-Schmiedeberg's Archives of Pharmacology, 2000, Vol 361, Issue 3, p319

0028-1298

Academic Journal

10.1007/s002109900187