Influence of nitric oxide derived from neuronal nitric oxide synthase on glomerular filtration

Abstract

The neuronal isoform of nitric oxide synthase (nNOS) has been localized to specific regions of the kidney, including the thick ascending limb of the loop of Henle and the macula densa. Because of this discrete localization in the renal cortex, nitric oxide (NO) produced by nNOS has been suggested to play an important role in the regulation of macula densa-mediated arteriole tone and therefore could play an important role in the regulation of whole-kidney glomerular filtration rate (GFR). We hypothesized that selective blockade of nNOS would decrease GFR. Renal hemodynamics were measured before and after acute selective blockade of nNOS by 50 mg/kg 7-nitroindazole (7-NI) in anesthetized rats. Administration of 7-NI had no significant effect on basal blood pressure (from 105 ± 3 to 101 ± 2 mm Hg), renal blood flow [from 6.08 ± 0.39 to 6.31 ± 0.33 ml/min/gram of kidney weight (gkw)], or total renal vascular resistance (from 18.1 ± 1.6 to 16.4 ± 1.0 mm Hg/ml/min/gkw) but decreased GFR by 26% (from 1.36 ± 0.15 to 1.00 ± 0.13 ml/min/gkw; p < 0.02), urinary flow rate by 28% (from 24.7 ± 1.8 to 17.8 ± 2.2 μl/min; p < 0.05), and sodium excretion by 22% (from 5.55 ± 0.53 to 4.30 ± 0.52 μEq/min; p < 0.05). However, fractional sodium excretion was not changed by nNOS inhibition. There were no such changes in vehicle-treated time controls. We conclude that, in the renal cortex, NO produced by nNOS plays an important role in the regulation of whole-kidney GFR and excretion in normal, sodium-replete rats.