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Aldose reductase inhibition reduces endothelial dysfunction and oxidative stress in skeletal muscle arterioles exposed to hyperglycemia
Author(s) -
Toth Erika,
Bagi Zsolt,
Racz Anita,
Koller Akos
Publication year - 2007
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.21.6.a834-a
Subject(s) - polyol pathway , aldose reductase , medicine , endocrinology , chemistry , oxidative stress , endothelial dysfunction , polyol , skeletal muscle , vasodilation , sodium nitroprusside , nitric oxide , diabetes mellitus , organic chemistry , polyurethane
We hypothesized that in hyperglycemia activation of polyol pathway, via increased production of sorbitol by the aldose reductase, contribute to the development of endothelial dysfunction. Thus the role of polyol pathway on vasomotor function in isolated rat skeletal muscle arterioles (~150 μm, at 80 mmHg) was investigated. Compared to controls (5 mM glucose, CG), high glucose treatment (HG, 25 mM glucose for 60 min) reduced flow (0–40 μL/min)‐ and sodium nitroprusside (SNP, 10 −9 –10 −6 M)‐induced dilations (flow: CG max: 39 ±2 μm, HG max: 15 ±1μm; SNP: control max: 41 ±2μm, HG max: 33 ±2μm), whereas adenosine (10 −7 –10 −4 M)‐induced dilations remained intact (CG max.: 42 ±1μm, HG max: 42 ±2μm). Presence of the aldose reductase inhibitor (ARI, zopolrestat, 10 μM) did not affect responses of CG arterioles, but mitigated HG‐induced decreases in flow‐induced dilations (HG + ARI max: 27 ±2μm), and also ameliorated impaired SNP‐induced dilations (HG + ARI max: 38 ±1μm) of HG arterioles. Also, compared to control there was increased superoxide production, indicated by ethidium bromide fluorescence, in HG treated femoral arteries, which was reduced by ARI. Thus we suggest that, increased activation of polyol pathway via increasing oxidative stress could contribute to the development of hyperglycemia‐induced arteriolar dysfunction. Supported by AHA NE Aff. 0555897T and Hungarian NSRF/OTKA ‐T48376, HSC/ETT 364/2006 and Zsigmond Diabetes Found: 711‐Dr.Koller/84289.