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

The neuronal isoform of nitric oxide synthase (nNOS) has been localized to specific regions of the kidney, including the thick ascending limb of the l oop of Henle and the macula dense. 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 arteriol e tone and therefore could play an important role in the regulation of whol e-kidney glomerular filtration rate (GFR). We hypothesized that selective b lockade 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 fl ow [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 +/- 0.1 3 ml/min/gkw; p < 0.02), urinary flow rate by 28% (from 24.7 +/- 1.8 to 17. 8 +/- 2.2 mu l/min; p < 0.05), and sodium excretion by 22% (from 5.55 +/- 9 .53 to 4.30 +/- 0.52 mu Eq/min; P < 0.05). However, fractional sodium excre tion was not changed by nNOS inhibition. There were no such changes in vehi cle-treated time controls. We conclude that, in the renal cortex, NO produc ed by nNOS plays an important role in the regulation of whole-kidney GFR an d excretion in normal, sodium-replete rats. (C) 2000 Elsevier Science Inc. All rights reserved.