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AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 6 1768-R1774, Copyright © 1997 by American Physiological Society
ARTICLES |
J. F. Reckelhoff, J. A. Kellum Jr, L. C. Racusen and D. A. Hildebrandt
Department of Physiology, University of Mississippi Medical Center, Jackson 39216, USA.
Aging is associated with loss of nephron function and reductions in serum L-arginine and excretion of nitric oxide (NO) metabolites. The present study was performed to determine if long-term dietary treatment with L-arginine, the NO synthase substrate, could prevent age-related renal 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 urinary nitrate/nitrite decreased with age in controls, but, during L-arginine treatment, urinary protein decreased and nitrate/nitrite increased. Two weeks after L-arginine was stopped, urinary protein had increased and nitrate/nitrite had decreased to the same level as in controls. L-Arginine treatment increased glomerular filtration rate (GFR) by 50% compared with untreated controls. In contrast, nitrite had no effect on GFR. Morphologically, L-arginine protected against aging injury by reducing the number of sclerotic glomeruli. In summary, we found that L-arginine prevented the age-related glomerular injury and reduction in GFR. The mechanism of protection, however, may be independent of NO.
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