Abstract

Several studies using SHRs failed to demonstrate the pressor effect of alcohol. In other studies chronic alcohol administration resulted in the attenuation of the development of hypertension in SHR or stroke-prone SHR. Although it was shown that alcohol administration caused a mild reduction in blood pressure still the mechanism of action is not understood. Indirect evidence from human studies had shown that the pressor effect of acute and chronic alcohol consumption may be due to the alteration of intracellular calcium accumulation. Preliminary studies suggest that chronic alcohol consumption in WKY and SH rats suppresses blood pressure, heart rate, and increased histamine levels which may involve a shift in intracellular calcium or increased entry of calcium into cardiovascular vessels through the regulation of voltage- activated calcium channels. However, the involvement of chronic alcohol consumption on the alteration of intracellular Ca2+ in hypertensive individuals is not clearly understood. We hypothesize that the tolerance and desensitivity of cardiovascular vessels to chronic alcohol exposure is mediated by changes in calcium transport into vascular smooth muscle. To test this hypothesis the following studies were proposed: 1. Effects of chronic and acute ethanol exposure on Ca2+ transients in SHR and WKY arterial (aorta rings) smooth muscle will be investigated. (Hypothesis: Chronic ethanol exposure affects the intracellular accumulation of Ca2+ in vascular smooth muscle of SH rats). 2. Data from Ca2+ influx of arterial smooth muscle will be correlated with data from the effects of ethanol on heart rate, mean arterial blood pressure, and histamine levels of chronic and acute exposed SHR and WKY rats. (Hypothesis: Chronic ethanol exposure alters the Ca2+ transport mechanism in vascular smooth muscle affecting blood pressure, heart rate, and histamine levels. 3. Changes in responsiveness of vascular smooth muscle (aorta) of SHR and WKY rats to chronic and acute ethanol exposure will be studied. (Hypothesis: Chronic alcohol (ethanol) exposure augments Ca2+ efflux affecting the relaxation of vascular smooth muscle in SH rats).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR011808-05
Application #
6353708
Study Section
Project Start
2001-09-30
Project End
2002-09-29
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
2000
Total Cost
$255,687
Indirect Cost

  Institution

Name
Tennessee State University
Department
Type
DUNS #
108814179
City
Nashville
State
TN
Country
United States
Zip Code
37209

  Publications

Johnson, A L; Goode, G D; Mtshali, C et al. (2007) Protein Kinase C- alpha/betaII, delta, and zeta/lambda involvement in ethanol-induced MAPK expression in vascular smooth muscle cells. Cell Mol Biol (Noisy-le-grand) 53:38-44
Jones, C D; Bartee, J A; Leite-Browning, M L et al. (2007) Methamphetamine-induced locomotor activity and behavioral sensitization: are dopamine d3 receptors involved? Cell Mol Biol (Noisy-le-grand) 53:15-22
Shaw, J B; Cai, Q; Mtshali, C et al. (2007) Heterogeneity of histamine H3 receptor genomic expression in the cerebral cortex of spontaneously hypertensive rat. Cell Mol Biol (Noisy-le-grand) 53:45-50
Cao, Z; Wang, Y; McAdory, B S et al. (2006) Identification and characterization of syntaxin 1 antisense variants in Limulus polyphemus. Cell Mol Neurobiol 26:53-66
Washington, Benny; Williams, Shunta; Armstrong, Patrice et al. (2006) Cadmium toxicity on arterioles vascular smooth muscle cells of spontaneously hypertensive rats. Int J Environ Res Public Health 3:323-8
Washington, B; Mtshali, C; Williams, S et al. (2003) Ethanol-induced mitogen activated protein kinase activity mediated through protein kinase C. Cell Mol Biol (Noisy-le-grand) 49:1351-6
Reid, Easton A; Cao, Zheng; Wang, Yilun et al. (2003) Molecular cloning and identification of a putative PKC epsilon cDNA from Limulus polyphemus brain. Life Sci 72:961-76
Ivy, M T; Newkirk, R F; Karim, M R et al. (2001) Hemicholinium-3 mustard reveals two populations of cycling choline cotransporters in Limulus. Neuroscience 102:969-78
Washington, B; Butler, K; Doye, A A et al. (2001) Heart function challenged with beta-receptor agonism or antagonism in a heart failure model. Cardiovasc Drugs Ther 15:479-86
Washington, B; Shaw, J B; Li, J et al. (2000) In vivo histamine release from brain cortex: the effects of modulating cellular and extracellular sodium and calcium channels. Eur J Pharmacol 407:117-22

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