LONG-TERM DIETARY SUPPLEMENTATION WITH L-ARGININE PREVENTS AGE-RELATED REDUCTION IN RENAL-FUNCTION

Aging is associated with loss of nephron function and reductions in se rum L-arginine and excretion of nitric oxide (NO) metabolites. The pre sent study was performed to determine if long-term dietary treatment w ith L-arginine, the NO synthase substrate, could prevent age-related r enal injury. Studies were performed in four groups of rats, aged 12-13 mo, for 8 mo: group 1 received L-arginine (2% in 2.5% corn syrup, n = 5); group 2 received sodium nitrite, an NO donor (0.1%, in 2.5% syrup , n = 7); group 3 was an untreated control group (n = 7); group 4 was treated with 2.5% corn syrup (n = 5). Urinary protein increased and ur inary nitrate/nitrite decreased with age in controls, but, during L-ar ginine treatment, urinary protein decreased and nitrate/nitrite increa sed. Two weeks after L-arginine was stopped, urinary protein had incre ased and nitrate/nitrite had decreased to the same level as in control s. L-Arginine treatment increased glomerular filtration rate (GFR) by 50% compared with untreated controls. In contrast, nitrite had no effe ct on GFR. Morphologically, L-arginine protected against aging injury by reducing the number of sclerotic glomeruli. In summary, we found th at L-arginine prevented the age-related glomerular injury and reductio n in GFR. The mechanism of protection, however. may be independent of NO.