RENAL HEMODYNAMIC-EFFECTS OF DIETARY-PROTEIN IN THE RAT - ROLE OF NITRIC-OXIDE

The biologic mediator(s) of the renal hemodynamic effects of a high di etary protein intake (hyperfiltration and renal vasodilation) are unkn own. The endogenous nitrovasodilator nitric oxide (NO) derives from th e amino acid L-arginine, and NO has been demonstrated to mediate the h yperfiltration and vasodilation observed during amino acid infusion in rats. We therefore hypothesized that NO may also mediate the longterm renal hemodynamic effects of variations in dietary protein intake. We studied rats maintained with low protein (6%) and high-protein (50%) diets for 2 weeks. An additional group of rats receiving a high-protei n diet was also treated with the NO synthase inhibitor, L-nitro-argini ne-methyl ester (NAME, 100 mg per liter of drinking water). After 2 we eks a high-protein diet was associated with a significant increase in glomerular filtration rate (GFR) (50% protein group vs 6% protein grou p, 1.01 +/- 0.03 vs 0.61 +/- 0.03 ml/min; p < 0.05) and renal vasodila tion (renal vascular resistance: 50% protein group vs 6% protein group , 11.70 +/- 0.88 vs 17.65 +/- 1.55 mm Hg/min/ml; p < 0.05) compared wi th a low-protein diet. Urinary excretion of the biologic markers of NO activity, nitrite and nitrate, were significantly increased in parall el to the increase in protein intake (50% protein group vs 6% protein group, 4.25 +/- 0.32 vs 2.55 +/- 0.26 nmol/ml GFR; p < 0.05). Inhibiti on of NO synthase blunted the increase in GFR (50% protein plus NAME g roup, 0.85 +/- 0.06 ml/min), prevented renal vasodilation (renal vascu lar resistance, 50% protein plus NAME group, 25.30 +/- 2.98 mm Hg/min/ ml; p < 0.05 vs 50%), and prevented the increased urinary nitrite and nitrate excretion rate during intake of a high-protein diet (50% prote in plus NAME group, 2.84 +/- 0.23 nmol/ml GFR; p < 0.05 vs 50% protein ; p not significant vs 6% protein). We conclude that enhanced activity of the endogenous NO system may mediate, at least in part, the renal hemodynamic effects of increased dietary protein intake.