Influence of circadian time, ageing, and hypertension on the urinary excretion of nitric oxide metabolites in rats

Urinary excretion of NO metabolites (NOx) was measured in male spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY) in two age groups: young (11 weeks) and old (58 weeks). Urine was collected every 6 h throughout 24 h with and without injection interperitoneally of N(G)-nitro-L-arginine-methyl-ester (L-NAME), 30 mg/kg, at 7:00 or 19:00 h. In addition, blood pressure changes by L-NAME were evaluated using radiotelemetry. In both strains of rats, injection of L-NAME abolished almost completely the urinary excretion of NOx, indicating that urinary NOx indeed reflect the endogenous rate of NO synthesis. Time-dependent variation in urinary NOx excretion was observed in WKY rats of both ages (analysis of variance, P<0.05), with higher excretion in the dark period. In SHR rats, time-dependent variation in NOx excretion was lost, and the overall amount of NOx excreted within 24 h was significantly lower in young SHR than in age-matched WKY rats. Moreover, blood pressure increases by L-NAME were significantly smaller in SHR than in WKY rats. In old rats of both strains, NOx excretion was reduced, and the difference between the strains disappeared. Our findings demonstrate that ageing is accompanied by a loss in NOx excretion, and suggest that hypertension in SHR leads to a reduction in NO synthesis already at young age.