We have previously shown that aging is associated with increased lipid pero
xidation, 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 increas
e in inducible nitric oxide synthase (iNOS) with aging, and if so, whether
inhibition of iNOS would prevent aging injury by preventing free radical-me
diated 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 plasm
a now by 40%, whereas glomerular sclerosis was considerably reduced. Renal
F-2-isoprostanes and malondialdehyde levels, markers of oxidative stress an
d lipid peroxidation, were not reduced by aminoguanidine. Aminoguanidine al
so did not attenuate immunostaining for advanced glycosylation end products
(AGE) in the kidneys. These findings suggest that aminoguanidine attenuate
s aging renal dysfunction by inhibiting a pathophysiologic function of iNOS
that is independent of free radical-mediated lipid peroxidation or signifi
cant effects on AGE deposition. (C) 1999 American Journal of Hypertension,