RENAL EFFECTS OF PROLONGED SYNTHESIS INHIBITION OF ENDOTHELIUM-DERIVED NITRIC-OXIDE

The aim of the present study was to investigate in conscious dogs the long-term effects of nitric oxide synthesis inhibition on glomerular filtration rate, sodium and water excretion, and plasma levels of renin and aldosterone. After a control period of 3 days, an inhibitor of endothelium-derived nitric oxide synthesis, N(G)-nitro-L-arginine-methyl ester, was infused for 3 consecutive days at a dose (50 ng/kg/min) that did not induce significant changes in arterial pressure (n=6). The inhibition of nitric oxide synthesis led to a large and sustained decrease (p<0.05) in glomerular filtration rate of approximately 35%. This change was accompanied by a decrease (p<0.05) in urinary sodium excretion from 78.9+/-4.6 meq/day to 49.8+/-6.8, 60.1+/-4.2, and 53.5+/-9.0 meq/day by days 1, 2, and 3 of nitric oxide synthesis inhibition, respectively. Changes in fractional sodium excretion failed to achieve statistical significance. Nitric oxide synthesis inhibition also induced a significant and sustained decrease in urine flow rate. The decrease in glomerular filtration rate, natriuresis, and diuresis was accompanied by a 45% increase in plasma renin activity (p<0.05) and no change in plasma aldosterone concentration. By day 3 of the recovery period, glomerular filtration rate, natriuresis, diuresis, and plasma renin activity returned to values similar to those found during the control period. The administration of L-arginine during 3 consecutive days (5-mu-g/kg.min i.v.) did not modify any of the parameters measured but effectively prevented all the renal changes induced by the 3 days of nitric oxide synthesis inhibition. The results of this study indicate that the continuous endogenous formation of nitric oxide may play an important role in the long-term regulation of renal hemodynamic and renal excretory function. It is suggested that an increase in renin release may contribute to the renal changes induced by the inhibition of nitric oxide synthesis during 3 consecutive days.