Renal effects of prolonged synthesis inhibition of endothelium-derived nitric oxide.

Abstract

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, NG-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 less than 0.05) in glomerular filtration rate of approximately 35%. This change was accompanied by a decrease (p less than 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 less than 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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)