Aminoguanidine improves renal function and attenuates glomerular injury in aging rats

Aging is associated with increased renal inducible nitric oxide synthase (iNOS), lipid peroxidation and production of advanced glycosylation end products (AGE's). Aminoguanidine is an antioxidant, inhibits iNOS and also prevents production of AGE's. The present studies were performed to determine if long term aminoguanidine would protect against age-related renal injury. Aminoguanidine (0.1% in drinking water) was given for 9 months to middle-aged male rats (N=6) (untreated controls, N=6) as they aged to 22 months. Protein and nitrate/nitrite excretion were measured bimonthly. At 22 months, renal function was measured, and kidneys were removed for morphology, measurement of renal F₂-isoprostane and immunohistochemical detection of heme oxygenase. Aminoguanidine decreased proteinuria, suggesting renal protection, and decreased nitrate/nitrite excretion after 15 months of age, suggesting inhibition of iNOS. Functionally, aminoguanidine increased GFR and renal plasma flow by 65% and 43%, respectively. Structurally, glomerular sclerosis was attenuated. However, aminoguanidine did not prevent against age-related renal oxidation: i.e. no protection against induction of heme oxygenase and no decrease in F₂-isoprostane. These findings suggest that aminoguanidine attenuates aging renal injury probably through an AGE-mediated mechanism rather through a discreet anti-oxidant mechanism.