title: Long-term dietary supplementation with L-arginine prevents age-related reduction in renal function.
abstract: 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.
authors.affiliation: Department of Physiology, University of Mississippi Medical Center, Jackson 39216, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Reckelhoff
authors.forename: J A
authors.initials: JA
authors.lastname: Kellum
authors.forename: L C
authors.initials: LC
authors.lastname: Racusen
authors.forename: D A
authors.initials: DA
authors.lastname: Hildebrandt
mesh_terms: D000375:Aging / Q000502:physiology* / Q000652:urine; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004032:Diet; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D007678:Kidney Glomerulus / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000494:pharmacology / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D012598:Sclerosis; D013997:Time Factors
chemical_list: D009566:Nitrates; D009573:Nitrites; D001120:Arginine