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 p rogressive aging in rats and that a decrease in nitric oxide precursor , L-arginine, also decreases with aging. Urinary nitrate/nitrite excre tory rates and serum L-arginine levels were measured in male Sprague D awley rats, ranging in ages from 3 to 25 months. Proteinuria increased dramatically with aging. Conversely, urinary nitrate/nitrite excretio n decreased by 50% and 80% in rats, aged 12 months and 17 months, resp ectively. There was no further decrease in urinary nitrate/nitrite exc retion 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 d ecrease in GFR could not account for the decrease in urinary nitrate/n itrite excretion in the old rats. However, serum L-arginine levels wer e 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 m ay decrease with aging and that one mechanism by which nitric oxide pr oduction could be decreased with age is a lack of the endogenous subst rate, L-arginine. Because NO has been implicated to be involved in man y physiological processes, age-related decreases in NO production coul d have far-reaching adverse effects in the aging individual.