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Role of CYP2E1 in Impaired Nitric Oxide Synthase (NOS)‐Dependent Cerebral Vasodilation During Chronic Alcohol Consumption
Author(s) -
Sun Hong,
Arrick Denise M,
Mayhan William G
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.20.4.a294
Subject(s) - vasodilation , chemistry , endocrinology , xanthine oxidase , medicine , nitric oxide synthase , cyp2e1 , enos , nitric oxide , pharmacology , biochemistry , metabolism , enzyme , cytochrome p450
Nebraska Medical Center, Omaha, NE, 68198‐5850 Oxidative stress is associated with alcohol‐induced impairment of NOS‐dependent cerebral vasodilation. We determined whether CYP2E1 and xanthine oxidase contribute to impaired NOS‐dependent dilation of cerebral arterioles during alcohol consumption. Using a cranial window, we measured effects of topical application of a CYP2E1 inhibitor, diallyl sulfide, and a xanthine oxidase inhibitor, allopurinol, on responses of parietal pial arterioles to eNOS‐dependent agonists (Ach and ADP), a nNOS‐dependent agonist (NMDA), and a NOS‐independent agonist (nitroglycerin) in nonalcohol‐fed and 2‐3 months alcohol‐fed rats. Protein expression of CYP2E1 in parietal cortex and pial arterioles was measured by Western blot analysis. Response of pial arterioles to nitroglycerin was similar in nonalcohol‐fed and alcohol‐fed rats. Compared to nonalcohol‐fed rats, however, vasodilation to Ach (1 and 10 μM), ADP (10 and 100 μM), and NMDA (0.1 and 0.3 mM) was significantly less in alcohol‐fed rats. Topical application of diallyl sulfide (1 mM) did not alter vasodilation in nonalcohol‐fed rats, but significantly improved vasodilation to Ach, ADP, and NMDA in alcohol‐fed rats. The expression of CYP2E1 was not altered in parietal cortex and pial arterioles of alcohol‐fed rats. In addition, topical application of allopurinol (0.3 mM) had no effect on responses of cerebral arterioles in nonalcohol‐fed and alcohol‐fed rats. Our findings suggest that CYP2E1, but not xanthine oxidase, may play an important role in impaired NOS‐dependent dilatation of cerebral arterioles during alcohol consumption.