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L‐Arginine Alleviates Hyperglycemia‐Induced Vascular Inflammation In Diabetic Mice
Author(s) -
West Matthew B,
Ramana Kota V.,
Srivastava Satish K,
Bhatnagar Aruni
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a979
Subject(s) - polyol pathway , aldose reductase , medicine , endocrinology , diabetes mellitus , streptozotocin , oxidative stress , nitric oxide , inflammation , arginine , endothelial dysfunction , chemistry , biochemistry , amino acid
Cardiovascular complications of diabetes are associated with a decrease in nitric oxide (NO) bioavailability. In this study, we tested the hypothesis that enhancing NO production with L‐arginine (Arg) would mitigate diabetic vascular stress. Diabetes was induced by injecting mice with streptozotocin (STZ). Two weeks of treatment with Arg using osmotic pumps increased plasma NO x levels. Arg treatment of diabetic mice decreased triglycerides from 59.1 ± 18.1 to 116.1 ± 18.0 mg/dl in saline‐treated diabetic mice. Hyperglycemia increased superoxide generation 6‐fold in the aorta of diabetic compared with non‐diabetic mice as measured by dihydroethidium (DHE) staining. Arg treatment decreased DHE staining in diabetic mice. Diabetes also increased the plasma levels of soluble ICAM which were decreased by Arg treatment. Arg supplementation abolished diabetes‐induced increases in renal sorbitol, indicating inhibition of aldose reductase (AR). To determine the mechanism of AR inhibition, AR was immunoprecipitated from heart and Western blots were developed using anti‐protein glutathione antibodies. Arg treatment increased AR glutathiolation; indicating NO‐induced AR inhibition by glutathiolation. These observations demonstrate that treatment with Arg prevents activation of the polyol pathway and decreases vascular oxidative stress and systemic inflammation.