The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using Nω-monomethyl-L-arginine (L-NMMA, 110 μg/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 μL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 ± 1 to 128 ± 2 mm Hg; P< 0.05) and a modest reduction in renal plasma flow rate (4.4 ± 0.2 to 4.2 ±0.1 mL/min; P< 0.05), without change in glomerular filtration rate (1.16 ± 0.03 to 1.15 ± 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 μL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 ± 6 versus 33 ± 5%, L-NMMA versus vehicle; P< 0.05) and obliterated the renal hyperemic response (-7 ± 6 versus 16 ± 4%, L-NMMA versus vehicle; P < 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 ± 4 versus 30 ± 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 ± 6 versus 20 ± 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow. These results with mixed amino acids differed from those with glycine alone, presumably because the former was rich in L-arginine, the metabolic precursor for nitric oxide. For glycine-treated rats, urinary 3′,5′-cGMP excretion rates increased significantly in both vehicle- and L-NMMA-treated rats (6.1 ± 1.1 to 15.7 ± 2.4 and 7.9 ± 0.6 to 14.6 ± 0.6 pmol/min, respectively). In summary, nitric oxide appears to influence basal systemic, and to a lesser extent, basal renal vascular tone. Furthermore, the renal effects of mixed amino acids and glycine are, at least in part, sensitive to L-NMMA, suggesting that nitric oxide formation contributes to the renal vasodilation and hyperfiltration responses to acute amino acid infusion.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of the American Society of Nephrology|
|State||Published - Jun 1991|
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