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(Hypertension. 2000;35:602.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Vasopressin Does not Effect Hypertension Caused by Long-Term Nitric Oxide Inhibition

Presented in part as an abstract (Br J Pharmacol. 1997;122:203P).

Cécile Loichot; Catherine Cazaubon; Michèle Grima; Wybren De Jong; Dino Nisato; Jean-Louis Imbs; Mariette Barthelmebs

From the Institut de Pharmacologie, Faculté de Médecine, Université Louis Pasteur de Strasbourg (C.L., M.G., W.D.J., J.-L.I., M.B.) and Service d’Hypertension Artérielle, Maladies Vasculaires et Pharmacologie Clinique, Hôpitaux Universitaires de Strasbourg (J.-L.I.), Strasbourg, France, and Sanofi Recherche, Département Cardiovasculaire (C.C., D.N.), Montpellier, France.

Correspondence to Dr Mariette Barthelmebs, Institut de Pharmacologie, 11 rue Humann, 67085 Strasbourg Cedex, France. E-mail Mariette.Barthelmebs{at}pharmaco-ulp.u-strasbg.fr

Abstract—Nitric oxide attenuates both vasopressin-induced vasoconstriction and vasopressin release. We tested whether hypertension and renal dysfunction elicited by chronic inhibition of nitric oxide (NO) synthesis using N^G-nitro-L-arginine (L-NNA) could be mediated in part by vasopressin V_1A receptors. Male rats were treated orally for 6 weeks with L-NNA (15 mg/kg per day), a nonpeptide V_1A receptor antagonist (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 (SR 49059, 30 mg/kg per day), or a combination of SR 49059 and L-NNA (same doses), or they received no treatment. Both drugs were added to the food. Measurements were performed in conscious rats (urine collection in metabolic cages, tail-cuff arterial pressure) and at the end of the study in anesthetized rats (clearance measurements). L-NNA produced sustained hypertension, decreased glomerular filtration rate, and increased renal vascular resistance, plasma renin activity, and urinary albumin excretion. SR 49059 had no effect per se on these parameters and also did not attenuate the hypertension and renal dysfunction induced by L-NNA. Surprisingly, SR 49059 potentiated L-NNA–induced hypertension at the end of the 6-week treatment. However, the blood pressure response and the renal and mesenteric vasoconstriction elicited by exogenous vasopressin were attenuated in rats treated with SR 49059. L-NNA did not change plasma vasopressin concentration or 24-hour urinary vasopressin excretion. Our findings suggest that activation of vasopressin V_1A receptors does not contribute to the hypertension and renal dysfunction induced by chronic NO synthesis inhibition. They also document unchanged plasma vasopressin concentration in NO-deficient hypertension.

Key Words: hemodynamics • hypertension, experimental • N^G-nitro-L-arginine • receptors, vasopressin • SR 49059

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