NITRIC-OXIDE AND RENAL EFFECTS OF VOLUME EXPANSION IN CONSCIOUS MONKEYS

Experiments were performed to determine the effects of nitric oxide (N O) synthase inhibition on the renal responses to volume expansion in c onscious cynomolgus monkeys. All animals were volume expanded with 3% dextran in normal saline under three conditions: 1) during a control s tate, 2) during constant infusion of the NO synthase inhibitor N-G-nit ro-L-arginine methyl ester (L-NAME, 30 mu g.kg(-1).min(-1)), and 3) du ring simultaneous infusion of L-NAME and excess NO substrate L-arginin e (0.6 mg.kg(-1).min(-1)). The control volume expansion increased urin e flow from 0.27 +/- 0.05 to 0.94 +/- 0.28 ml/min and sodium excretion from 21 +/- 9 to 95 +/- 26 mu eg/min. During L-NAME infusion, these r esponses were attenuated in that urine flow only increased from 0.13 /- 0.03 to 0.28 +/- 0.09 ml/min and sodium excretion from 13 +/- 8 to 35 +/- 23 mu eg/min. Addition of L-arginine to the L-NAME infusion abo lished these renal excretory effects oft-NAME alone. With combined L-N AME/L-arginine, volume expansion increased urine flow from 0.37 +/- 0. 23 to 1.09 +/- 0.23 ml/min and sodium excretion from 38 +/- 27 to 150 +/- 24 mu eg/min, responses similar to control. L-Arginine also marked ly attenuated the effect of L-NAME to increase mean arterial pressure and abolished the L-NAME decreases in creatinine and p-aminohippurate clearances. However, an L-NAME-induced bradycardia could only be parti ally reversed. These results demonstrate that a functioning NO system may be important in mediating normal renal responses to volume expansi on in this primate species.