Chronic (heavy) consumption of alcohol has been recognized as a major contributing factor in the pathogenesis of many vascular diseases, including diseases of the brain. A large body of evidence suggests that chronic consumption of alcohol predisposes to the development of both hemorrhagic and thromboembolic stroke. Mechanisms by which chronic consumption of alcohol predispose to cerebrovascular abnormalities, including stroke, however, are not clear. The studies proposed in this application will determine the effects of chronic alcohol consumption on the cerebral microcirculation. The central hypothesis of this application is that chronic alcohol consumption predisposes to cerebrovascular abnormalities by altering cellular processes which modulate reactivity of cerebral blood vessels. To examine this central hypothesis, we will conduct two series of experiments. The first series of experiments will examine the temporal effect of chronic alcohol consumption on important cellular signaling pathways (nitric oxide synthase, ATP-sensitive potassium channels and adenylate cyclase which produce dilatation of cerebral arterioles. We will also determine the mechanisms which may account for impaired dilatation of cerebral arterioles during chronic alcohol consumption and examine the morphology of cerebral arterioles. The second series of experiments will examine the temporal effect of chronic alcohol consumption on the distribution of microvascular pressure in the cerebral circulation. We will examine the distribution of cerebral microvascular pressure under basal conditions and during changes in arterial pressure. We believe that these studies will provide the first comprehensive examination of the effects of chronic alcohol consumption on the cerebral microcirculation and will provide valuable insights into factors which contribute to the pathogenesis of cerebrovascular abnormalities, possibly ischemic and hemorrhagic stroke, during chronic alcohol consumption.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA011288-01A2
Application #
2765756
Study Section
Special Emphasis Panel (ZRG4-ALTX-4 (01))
Project Start
1999-01-01
Project End
2002-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
Qin, Lei; Schmidt, Ehud J; Tse, Zion Tsz Ho et al. (2013) Prospective motion correction using tracking coils. Magn Reson Med 69:749-59
Sun, Hong; Xiong, Wanfen; Arrick, Denise M et al. (2012) Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARýý. PLoS One 7:e41716
Mayhan, William G; Arrick, Denise M; Patel, Kaushik P et al. (2011) Exercise training normalizes impaired NOS-dependent responses of cerebral arterioles in type 1 diabetic rats. Am J Physiol Heart Circ Physiol 300:H1013-20
Arrick, Denise M; Sun, Hong; Patel, Kaushik P et al. (2011) Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats. Am J Physiol Heart Circ Physiol 301:H696-703
Zhao, Honggang; Mayhan, William G; Arrick, Denise M et al. (2011) Dose-related influence of chronic alcohol consumption on cerebral ischemia/reperfusion injury. Alcohol Clin Exp Res 35:1265-9
Arrick, Denise M; Mayhan, William G (2010) Inhibition of endothelin-1 receptors improves impaired nitric oxide synthase-dependent dilation of cerebral arterioles in type-1 diabetic rats. Microcirculation 17:439-46
Zhao, Honggang; Mayhan, William G; Arrick, Denise M et al. (2010) Alcohol-induced exacerbation of ischemic brain injury: role of NAD(P)H oxidase. Alcohol Clin Exp Res 34:1948-55
Ren, Caili; Du, Ailin; Li, Dongliang et al. (2010) Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats. Brain Res 1345:197-205
Mayhan, William G; Arrick, Denise M; Sun, Hong et al. (2010) Exercise training restores impaired dilator responses of cerebral arterioles during chronic exposure to nicotine. J Appl Physiol (1985) 109:1109-14
Mayhan, William G; Arrick, Denise M; Sharpe, Glenda M et al. (2009) Nitric oxide synthase-dependent responses of the basilar artery during acute infusion of nicotine. Nicotine Tob Res 11:270-7

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