Changes in nitric oxide precursor, L-arginine, and metabolites, nitrate and nitrite, with aging.

The present study was performed to test the hypothesis that excretion of nitric oxide metabolites, nitrate and nitrite, are decreased with progressive aging in rats and that a decrease in nitric oxide precursor, L-arginine, also decreases with aging. Urinary nitrate/nitrite excretory rates and serum L-arginine levels were measured in male Sprague Dawley rats, ranging in ages from 3 to 25 months. Proteinuria increased dramatically with aging. Conversely, urinary nitrate/nitrite excretion decreased by 50% and 80% in rats, aged 12 months and 17 months, respectively. There was no further decrease in urinary nitrate/nitrite excretion in very old rats, aged 23-24 months. Glomerular filtration rate (GFR) was also measured in some of the rats, aged 3-5 mos and 17 mos. GFR was not different between old and young rats, suggesting that a decrease in GFR could not account for the decrease in urinary nitrate/nitrite excretion in the old rats. However, serum L-arginine levels were decreased with aging, by 30% and 50% in rats, aged 13-15 months and 24-25 months, respectively, when compared with young rats. These data confirm our hypothesis and suggest that nitric oxide (NO) production may decrease with aging and that one mechanism by which nitric oxide production could be decreased with age is a lack of the endogenous substrate, L-arginine. Because NO has been implicated to be involved in many physiological processes, age-related decreases in NO production could have far-reaching adverse effects in the aging individual.