nitroarginine and Albuminuria

Experiments on Wistar rats showed that single intraperitoneal injection nonselective NO-synthase inhibitor L-NAME in a dose of 50 mg/kg was followed by transient proteinuria and albuminuria. This effect was not reproduced by injection of ODQ, an inhibitor of intracellular effects of NO, and arginine, but D-NAME, an optical isomer of L-NAME not blocking NO-synthase, produced similar, though less pronounced effect. The degree of proteinuria and albuminuria increased in combined treatment with nitroarginine methyl esters and 1-deamino-arginine vasotocin or arginine vasopressin. Proteinuria during treatment with arginine derivatives attests to not only their effect on the charge of the filtration membrane, but also the participation of NO-dependent processes in the regulation of ultrafiltration in renal glomeruli.

Topics: Albumins; Albuminuria; Animals; Arginine Vasopressin; Enzyme Inhibitors; Female; Kidney; Kidney Glomerulus; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Proteinuria; Rats; Rats, Wistar; Vasotocin

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.

Topics: Albuminuria; Animals; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Enzyme Inhibitors; Heart; Heart Rate; Hypertension; Indoles; Kidney; Male; Nitric Acid; Nitric Oxide Synthase; Nitroarginine; Organ Size; Pyrrolidines; Rats; Rats, Sprague-Dawley; Systole; Time Factors; Vasopressins