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Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat

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Abstract

The link between chronic alcohol consumption and cardiovascular injury including hypertension is well known. However, molecular mediators implicated with alcohol-induced elevation in blood pressure (BP) remain elusive. The aim of this study was to investigate the relationship of chronic ethanol-induced endothelial injury and elevation in BP with angiotensin II levels in rats. Male Fisher rats were divided into two groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) ethanol (4 g kg−1, orally) daily for 12 weeks. The BP (systolic, diastolic, and mean) was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; blood and thoracic aorta were isolated and analyzed for aortic reactivity response, angiotensin II levels, and oxidative endothelial injury. The results show that the systolic, diastolic, and mean BP were significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to elevated angiotensin II levels in the plasma and aorta of alcohol treated group compared to control. The aortic NADPH oxidase activity, ratio of oxidized to reduced glutathione (GSSG/GSH) and lipid peroxidation significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), and vascular endothelial growth factor (VEGF) protein expressions were depressed in alcohol group compared to control. The phenylephrine-mediated vasoconstriction response was not altered, while acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol treated rats compared to control. It is concluded that chronic ethanol ingestion induces hypertension which is correlated with elevated tissue angiotensin II levels, activation of NADPH oxidase activity causing endothelial injury, depletion of endothelial NO generating system, and impaired vascular relaxation in rats.

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Acknowledgment

This work was supported in part by RCMI NIH grant # 2G12RR03050-19.

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Authors and Affiliations

  1. Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, P.O. Box 7004, Ponce, PR, 00732, USA

    Kazim Husain, Manuel Vazquez & Jainarine Lalla

  2. Department of Biology, Cuyahoga Community College, Parma Heights, OH, USA

    Rais A. Ansari

  3. Moffitt Cancer Center, University of South Florida, Tampa, FL, USA

    Mokenge P. Malafa

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  1. Kazim Husain
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  2. Manuel Vazquez
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  3. Rais A. Ansari
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  4. Mokenge P. Malafa
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  5. Jainarine Lalla
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Correspondence to Kazim Husain.

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Husain, K., Vazquez, M., Ansari, R.A. et al. Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat. Mol Cell Biochem 307, 51–58 (2008). https://doi.org/10.1007/s11010-007-9583-6

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  • DOI: https://doi.org/10.1007/s11010-007-9583-6

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