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Effects of NADH and NADPH on superoxide levels and cerebral vascular tone.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Didion, Sean P. Faraci, Frank M. |
| Copyright Year | 2002 |
| Abstract | Reactive oxygen species are important modulators of cerebral vascular tone. Recent evidence, mainly from the aorta, suggests that NAD(P)H oxidase is a major source of vascular superoxide. The goal of the present study was to examine the effects of NADH and NADPH that are commonly used to stimulate NAD(P)H oxidase activity, on superoxide levels and cerebral vascular tone. Basilar arteries and cerebral arterioles from normal rabbits were studied in vitro using isolated tissue baths and in vivo using a cranial window, respectively. In the basilar artery, NADH produced a biphasic response; low concentrations (0.1-10 microM NADH) produced marked relaxation, whereas higher concentrations (30-100 microM NADH) produced contraction. Responses to NADH were significantly (P < 0.05) inhibited in the presence of 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron; a scavenger of superoxide, 10 mM). In contrast, NADPH (10-100 microM) produced moderate contraction of the basilar artery, which was inhibited in the presence of Tiron. In vivo, NADH produced Tiron-sensitive dilatation of cerebral arterioles. NADH and NADPH dose dependently increased superoxide levels in the basilar artery, as detected by lucigenin (5 microM)-enhanced chemiluminescence, but increases in superoxide were significantly greater for NADPH than NADH. These increases in superoxide were markedly reduced in the presence of polyethylene glycol-superoxide dismutase (300 U/ml) or diphenylene iodonium [0.1 mM, an inhibitor of flavin-containing enzymes, including NAD(P)H oxidase] but were not affected by indomethacin, N(G)-nitro-L-arginine, or allopurinol. These data suggest that NADH- and NADPH-induced changes in cerebral vascular tone are mediated by superoxide, produced by a flavin-containing enzyme, most likely NAD(P)H oxidase, but not xanthine oxidase or nitric oxide synthase. |
| Starting Page | 49 |
| Ending Page | 55 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpheart.physiology.org/content/ajpheart/282/2/H688.full.pdf |
| PubMed reference number | 11788419v1 |
| Volume Number | 282 |
| Issue Number | 2 |
| Journal | American journal of physiology. Heart and circulatory physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt 4,6-dinitro-o-cresol Allopurinol Aorta Arginine Arteries Bathing Chemiluminescence Dilate procedure Gas Scavengers In Vitro [Publication Type] Indomethacin Lucigenin Monoamine Oxidase NADH Nitric Oxide Synthase Polyethylene Glycols Reactive Oxygen Species Structure of arteriole Structure of basilar artery Subclavian Steal Syndrome Superoxide Dismutase Superoxides Thioctic Acid Xanthine Oxidase diphenyleneiodonium |
| Content Type | Text |
| Resource Type | Article |
