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Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats.

Reckelhoff JF, Hennington BS, Kanji V, Racusen LC, Schmidt AM, Yan SD, Morrow J, Roberts LJ, Salahudeen AK
Am J Hypertens. 1999 12 (5): 492-8

PMID: 10342787 · DOI:10.1016/s0895-7061(98)00264-7

We have previously shown that aging is associated with increased lipid peroxidation, reductions in renal function, and increased glomerular sclerosis. The mechanism(s) responsible for these age-related changes are not clear. The purpose of the present studies was to determine if there was an increase in inducible nitric oxide synthase (iNOS) with aging, and if so, whether inhibition of iNOS would prevent aging injury by preventing free radical-mediated lipid peroxidation. iNOS protein expression in the kidney increased by approximately 90% by 24 months. Inhibition of iNOS by aminoguanidine (0.1% in drinking water) for 9 months, beginning at 13 months of age, reduced blood pressure, improved glomerular filtration rate by 70%, and renal plasma flow by 40%, whereas glomerular sclerosis was considerably reduced. Renal F2-isoprostanes and malondialdehyde levels, markers of oxidative stress and lipid peroxidation, were not reduced by aminoguanidine. Aminoguanidine also did not attenuate immunostaining for advanced glycosylation end products (AGE) in the kidneys. These findings suggest that aminoguanidine attenuates aging renal dysfunction by inhibiting a pathophysiologic function of iNOS that is independent of free radical-mediated lipid peroxidation or significant effects on AGE deposition.

MeSH Terms (23)

Aging Animals Biomarkers Blotting, Western Dinoprost Disease Models, Animal Enzyme Inhibitors F2-Isoprostanes Follow-Up Studies Glomerular Filtration Rate Glomerulosclerosis, Focal Segmental Glycation End Products, Advanced Guanidines Kidney Lipid Peroxidation Male Malondialdehyde Nitric Oxide Synthase Nitric Oxide Synthase Type II Oxidative Stress Rats Rats, Sprague-Dawley Renal Plasma Flow

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