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 dietary protein intake (hyperfiltration and renal vasodilation) are unknown. The endogenous nitrovasodilator nitric oxide (NO) derives from the amino acid L-arginine, and NO has been demonstrated to mediate the hyperfiltration 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-protein diet was also treated with the NO synthase inhibitor, L-nitro-arginine-methyl ester (NAME, 100 mg per liter of drinking water). After 2 weeks a high-protein diet was associated with a significant increase in glomerular filtration rate (GFR) (50% protein group vs 6% protein group, 1.01 +/- 0.03 vs 0.61 +/- 0.03 ml/min; p < 0.05) and renal vasodilation (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 with a low-protein diet. Urinary excretion of the biologic markers of NO activity, nitrite and nitrate, were significantly increased in parallel 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). Inhibition of NO synthase blunted the increase in GFR (50% protein plus NAME group, 0.85 +/- 0.06 ml/min), prevented renal vasodilation (renal vascular 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% protein 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.