Journal
MICROCIRCULATION
Volume 15, Issue 3, Pages 225-236Publisher
WILEY
DOI: 10.1080/10739680701641421
Keywords
adenosine diphosphate; acetylcholine; nitroglycerin; brain; nitric oxide; rats; apocynin; tempol; DPI
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Funding
- NHLBI NIH HHS [R01 HL090657, R01 HL090657-03, HL 79587] Funding Source: Medline
- NIAAA NIH HHS [AA 11288] Funding Source: Medline
- NIDA NIH HHS [DA 14258] Funding Source: Medline
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Objective: Our goal was to identify the role of oxidative stress via activation of NAD(P)H oxidase in cerebrovascular dysfunction in aged rats. Methods: We examined the reactivity of cerebral arterioles in adult and aged Fisher-344 rats to endothelial nitric oxide synthase (eNOS)-dependent (acetylcholine and adenosine diphosphate [ADP]) and -independent (nitroglycerin) agonists before and during application of tempol, apocynin, and diphenyleneiodonium chloride (DPI). We used Western blot to examine subunits of NAD(P)H oxidase, eNOS, and superoxide dismutase (SOD-l) in cerebral microvessels and parietal cortex. Finally, we measured superoxide production by cortex tissue in adult and aged rats. Results: Acetylcholine- and ADP-induced, but not nitroglycerin-induced, dilatation of cerebral arterioles was impaired in aged compared to adult rats. While tempol, apocynin, and DPI did not alter responses in adults, they alleviated impaired eNOS-dependent vasodilatation in aged rats, without influencing responses to nitroglycerin. eNOS and p67phox proteins were increased in cerebral microvessels from aged compared to adult rats. Further, p67phox and gp91phox proteins were increased, but SOD-1 protein was decreased, in cortex tissue of aged rats. Basal and agonist-induced production of superoxide was elevated in aged rats. Conclusions: Aging impairs eNOS-dependent reactivity of cerebral arterioles via an increase in superoxide produced by activation of NAD(P)H oxidase.
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