Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats

Citation
Jf. Reckelhoff et al., Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats, AM J HYPERT, 12(5), 1999, pp. 492-498
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
AMERICAN JOURNAL OF HYPERTENSION
ISSN journal
0895-7061 → ACNP
Volume
12
Issue
5
Year of publication
1999
Pages
492 - 498
Database
ISI
SICI code
0895-7061(199905)12:5<492:CAARDA>2.0.ZU;2-C
Abstract
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, Ltd.