Renal effects of nitric oxide synthase inhibition in conscious water-loaded dogs

Abstract

The renal effects of the nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester (l-NAME) were investigated in conscious dogs undergoing sustained water diuresis and replacement of urinary sodium losses. Experiments were performed with and without additional extracellular volume expansion (isotonic saline, 2% body wt). l-NAME (10 μg · kg−1 · min−1) infused during water diuresis decreased urine flow (2.5 ± 0.2 to 1.5 ± 0.3 ml/min), free water clearance (1.9 ± 0.2 to 1.0 ± 0.2 ml/min), and sodium excretion (4.0 ± 1.7 to 2.1 ± 0.6 μmol/min). Arterial blood pressure increased from 112 ± 2 to 126 ± 3 mmHg, but creatinine clearance did not measurably change. Plasma endothelin and vasopressin concentrations and plasma renin activity (PRA) were unchanged. Urinary endothelin concentration increased (3.4 ± 0.8 to 6.2 ± 1.7 pg/ml), but the excretion rate remained constant. l-Arginine infusion (0.6 mg · kg−1 · min−1) along withl-NAME abolished the renal effects but not the blood pressure increase. Volume expansion increased urine flow (2.5 ± 0.4 to 5.7 ± 0.5 ml/min) and sodium excretion (3.8 ± 1.6 to 76.5 ± 14.5 μmol/min). l-NAME attenuated the renal effects of volume expansion: urine flow increased to 2.8 ± 0.7 ml/min and sodium excretion to 34 ± 17 μmol/min. PRA decreased with control volume expansion but not during l-NAME. Urinary endothelin levels were elevated by l-NAME, decreased with volume expansion in all series, but excretion rate remained constant. Infusion of l-arginine partially reversed these effects of l-NAME. The results demonstrate that NO synthase inhibition increases blood pressure and blunts the renal responses to water and saline loading.