Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus

N. Ishii, Kaushik P Patel, P. H. Lane, T. Taylor, K. Bian, F. Murad, J. S. Pollock, Pamela K Carmines

Research output: Contribution to journalArticle

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Abstract

Experiments were performed to test the hypothesis that diabetes mellitus disrupts the balance between synthesis and degradation of nitric oxide (NO) in the renal cortex. Diabetes was induced by injection of streptozotocin, and sufficient insulin was provided to maintain moderate hyperglycemia for the ensuing 2 wk. Despite an 80% increase in total NO synthase activity measured by L-citrulline assay, nicotinamide adenine dinucleotide phosphate-diaphorase staining was unaltered, and no changes in NO synthase isoform protein levels or their distribution were evident in renal cortex from diabetic rats. Superoxide anion production was accelerated twofold in renal cortical slices from diabetic rats, with an associated 50% increase in superoxide dismutase activity. Western blots prepared by use of a monoclonal antinitrotyrosine antibody revealed an approximately 70-kD protein in renal cortex from sham rats, the nitrotyrosine content of which was threefold greater in cortical samples from diabetic rats. These observations indicate that the early stage of diabetes mellitus provokes accelerated renal cortical superoxide anion production in a setting of normal or increased NO production. This situation can be expected to promote peroxynitrite formation, resulting in the tyrosine nitration of a single protein of unknown identity, as well as a decline in the bioavailability of NO. These events are consistent with the postulate that oxidative stress promotes NO degradation in the renal cortex during the early stage of diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)1630-1639
Number of pages10
JournalJournal of the American Society of Nephrology
Volume12
Issue number8
StatePublished - Aug 4 2001

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Diabetes Mellitus
Nitric Oxide
Oxidative Stress
Kidney
Nitric Oxide Synthase
Superoxides
Citrulline
Peroxynitrous Acid
Streptozocin
NADP
Hyperglycemia
Biological Availability
Superoxide Dismutase
Tyrosine
Protein Isoforms
Proteins
Western Blotting
Monoclonal Antibodies
Insulin
Staining and Labeling

ASJC Scopus subject areas

  • Nephrology

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Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus. / Ishii, N.; Patel, Kaushik P; Lane, P. H.; Taylor, T.; Bian, K.; Murad, F.; Pollock, J. S.; Carmines, Pamela K.

In: Journal of the American Society of Nephrology, Vol. 12, No. 8, 04.08.2001, p. 1630-1639.

Research output: Contribution to journalArticle

Ishii, N. ; Patel, Kaushik P ; Lane, P. H. ; Taylor, T. ; Bian, K. ; Murad, F. ; Pollock, J. S. ; Carmines, Pamela K. / Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus. In: Journal of the American Society of Nephrology. 2001 ; Vol. 12, No. 8. pp. 1630-1639.
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