Dietary cholesterol protects against alcohol-induced cerebral artery constriction

Research output: Contribution to journalArticle

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Abstract

Background: Binge drinking represents the major form of excessive alcohol (ethanol [EtOH]) consumption in the United States. Episodic (such as binge) drinking results in blood alcohol levels (BAL) of 18 to 80 mM and leads to alcohol-induced cerebral artery constriction (AICAC). AICAC was shown to arise from EtOH-induced inhibition of large-conductance, calcium/voltage-gated potassium (BK) channels in the vascular smooth muscle. Factors that modulate BK channel-mediated AICAC remain largely unknown. Methods: Male Sprague Dawley rats were placed on high-cholesterol (2% of cholesterol) diet for 18 to 23 weeks. Their littermates were placed on control iso-caloric diet. AICAC was evaluated both in vivo and in vitro, by means of pial arteriole diameter monitoring through a closed cranial window and diameter measurements of isolated, pressurized cerebral arteries. Cholesterol level in the cerebral artery tissue was manipulated by methyl-β-cyclodextrin to reverse dietary-induced accumulation of cholesterol. BK channel surface presence on the plasma membrane of cerebral artery myocytes was evaluated by immunofluorescence staining. BK channel function in pressurized cerebral artery was assessed using selective BK channel blocker paxilline. Results: Within 5 minutes of 50 mM EtOH injection into carotid artery in vivo, arteriole diameter decreased by 20% in control group. Pial arteriole constriction was significantly reduced in rats on high-cholesterol diet, resulting in only 10% reduction in diameter. BAL in both groups, however, remained the same. Significant reduction in AICAC in group on high-cholesterol diet compared to control was also observed after middle cerebral artery dissection and in vitro pressurization at 60 mmHg, this reduction remaining after endothelium removal. Cholesterol level in de-endothelialized cerebral arteries was significantly increased in rats on high-cholesterol diet. Removal of excessive cholesterol content restored AICAC to the level observed in cerebral arteries of rats on normal diet. Immunofluorescence staining of BK channel-forming and accessory, smooth muscle-specific β1 subunit in freshly isolated cerebral artery myocyte showed that high-cholesterol diet did not down-regulate surface presence of BK protein. However, paxilline-induced cerebral artery constriction was diminished in arteries from rats on high-cholesterol diet. Conclusions: Our data indicate that dietary cholesterol protects against AICAC. This protection is caused by cholesterol buildup in the arterial tissue and diminished function (but not surface presence) of EtOH target-BK channel.

Original languageEnglish (US)
Pages (from-to)1216-1226
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number5
DOIs
StatePublished - Jan 1 2014

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Dietary Cholesterol
Cerebral Arteries
Constriction
Large-Conductance Calcium-Activated Potassium Channels
Cholesterol
Alcohols
Nutrition
Diet
Rats
Arterioles
Binge Drinking
Muscle
Blood
Muscle Cells
Fluorescent Antibody Technique
Tissue
Dissection
Pressurization
Staining and Labeling
Cyclodextrins

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Dietary cholesterol protects against alcohol-induced cerebral artery constriction. / Bukiya, Anna; Dopico, Alejandro; Leffler, Charles; Fedinec, Alexander.

In: Alcoholism: Clinical and Experimental Research, Vol. 38, No. 5, 01.01.2014, p. 1216-1226.

Research output: Contribution to journalArticle

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title = "Dietary cholesterol protects against alcohol-induced cerebral artery constriction",
abstract = "Background: Binge drinking represents the major form of excessive alcohol (ethanol [EtOH]) consumption in the United States. Episodic (such as binge) drinking results in blood alcohol levels (BAL) of 18 to 80 mM and leads to alcohol-induced cerebral artery constriction (AICAC). AICAC was shown to arise from EtOH-induced inhibition of large-conductance, calcium/voltage-gated potassium (BK) channels in the vascular smooth muscle. Factors that modulate BK channel-mediated AICAC remain largely unknown. Methods: Male Sprague Dawley rats were placed on high-cholesterol (2{\%} of cholesterol) diet for 18 to 23 weeks. Their littermates were placed on control iso-caloric diet. AICAC was evaluated both in vivo and in vitro, by means of pial arteriole diameter monitoring through a closed cranial window and diameter measurements of isolated, pressurized cerebral arteries. Cholesterol level in the cerebral artery tissue was manipulated by methyl-β-cyclodextrin to reverse dietary-induced accumulation of cholesterol. BK channel surface presence on the plasma membrane of cerebral artery myocytes was evaluated by immunofluorescence staining. BK channel function in pressurized cerebral artery was assessed using selective BK channel blocker paxilline. Results: Within 5 minutes of 50 mM EtOH injection into carotid artery in vivo, arteriole diameter decreased by 20{\%} in control group. Pial arteriole constriction was significantly reduced in rats on high-cholesterol diet, resulting in only 10{\%} reduction in diameter. BAL in both groups, however, remained the same. Significant reduction in AICAC in group on high-cholesterol diet compared to control was also observed after middle cerebral artery dissection and in vitro pressurization at 60 mmHg, this reduction remaining after endothelium removal. Cholesterol level in de-endothelialized cerebral arteries was significantly increased in rats on high-cholesterol diet. Removal of excessive cholesterol content restored AICAC to the level observed in cerebral arteries of rats on normal diet. Immunofluorescence staining of BK channel-forming and accessory, smooth muscle-specific β1 subunit in freshly isolated cerebral artery myocyte showed that high-cholesterol diet did not down-regulate surface presence of BK protein. However, paxilline-induced cerebral artery constriction was diminished in arteries from rats on high-cholesterol diet. Conclusions: Our data indicate that dietary cholesterol protects against AICAC. This protection is caused by cholesterol buildup in the arterial tissue and diminished function (but not surface presence) of EtOH target-BK channel.",
author = "Anna Bukiya and Alejandro Dopico and Charles Leffler and Alexander Fedinec",
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T1 - Dietary cholesterol protects against alcohol-induced cerebral artery constriction

AU - Bukiya, Anna

AU - Dopico, Alejandro

AU - Leffler, Charles

AU - Fedinec, Alexander

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: Binge drinking represents the major form of excessive alcohol (ethanol [EtOH]) consumption in the United States. Episodic (such as binge) drinking results in blood alcohol levels (BAL) of 18 to 80 mM and leads to alcohol-induced cerebral artery constriction (AICAC). AICAC was shown to arise from EtOH-induced inhibition of large-conductance, calcium/voltage-gated potassium (BK) channels in the vascular smooth muscle. Factors that modulate BK channel-mediated AICAC remain largely unknown. Methods: Male Sprague Dawley rats were placed on high-cholesterol (2% of cholesterol) diet for 18 to 23 weeks. Their littermates were placed on control iso-caloric diet. AICAC was evaluated both in vivo and in vitro, by means of pial arteriole diameter monitoring through a closed cranial window and diameter measurements of isolated, pressurized cerebral arteries. Cholesterol level in the cerebral artery tissue was manipulated by methyl-β-cyclodextrin to reverse dietary-induced accumulation of cholesterol. BK channel surface presence on the plasma membrane of cerebral artery myocytes was evaluated by immunofluorescence staining. BK channel function in pressurized cerebral artery was assessed using selective BK channel blocker paxilline. Results: Within 5 minutes of 50 mM EtOH injection into carotid artery in vivo, arteriole diameter decreased by 20% in control group. Pial arteriole constriction was significantly reduced in rats on high-cholesterol diet, resulting in only 10% reduction in diameter. BAL in both groups, however, remained the same. Significant reduction in AICAC in group on high-cholesterol diet compared to control was also observed after middle cerebral artery dissection and in vitro pressurization at 60 mmHg, this reduction remaining after endothelium removal. Cholesterol level in de-endothelialized cerebral arteries was significantly increased in rats on high-cholesterol diet. Removal of excessive cholesterol content restored AICAC to the level observed in cerebral arteries of rats on normal diet. Immunofluorescence staining of BK channel-forming and accessory, smooth muscle-specific β1 subunit in freshly isolated cerebral artery myocyte showed that high-cholesterol diet did not down-regulate surface presence of BK protein. However, paxilline-induced cerebral artery constriction was diminished in arteries from rats on high-cholesterol diet. Conclusions: Our data indicate that dietary cholesterol protects against AICAC. This protection is caused by cholesterol buildup in the arterial tissue and diminished function (but not surface presence) of EtOH target-BK channel.

AB - Background: Binge drinking represents the major form of excessive alcohol (ethanol [EtOH]) consumption in the United States. Episodic (such as binge) drinking results in blood alcohol levels (BAL) of 18 to 80 mM and leads to alcohol-induced cerebral artery constriction (AICAC). AICAC was shown to arise from EtOH-induced inhibition of large-conductance, calcium/voltage-gated potassium (BK) channels in the vascular smooth muscle. Factors that modulate BK channel-mediated AICAC remain largely unknown. Methods: Male Sprague Dawley rats were placed on high-cholesterol (2% of cholesterol) diet for 18 to 23 weeks. Their littermates were placed on control iso-caloric diet. AICAC was evaluated both in vivo and in vitro, by means of pial arteriole diameter monitoring through a closed cranial window and diameter measurements of isolated, pressurized cerebral arteries. Cholesterol level in the cerebral artery tissue was manipulated by methyl-β-cyclodextrin to reverse dietary-induced accumulation of cholesterol. BK channel surface presence on the plasma membrane of cerebral artery myocytes was evaluated by immunofluorescence staining. BK channel function in pressurized cerebral artery was assessed using selective BK channel blocker paxilline. Results: Within 5 minutes of 50 mM EtOH injection into carotid artery in vivo, arteriole diameter decreased by 20% in control group. Pial arteriole constriction was significantly reduced in rats on high-cholesterol diet, resulting in only 10% reduction in diameter. BAL in both groups, however, remained the same. Significant reduction in AICAC in group on high-cholesterol diet compared to control was also observed after middle cerebral artery dissection and in vitro pressurization at 60 mmHg, this reduction remaining after endothelium removal. Cholesterol level in de-endothelialized cerebral arteries was significantly increased in rats on high-cholesterol diet. Removal of excessive cholesterol content restored AICAC to the level observed in cerebral arteries of rats on normal diet. Immunofluorescence staining of BK channel-forming and accessory, smooth muscle-specific β1 subunit in freshly isolated cerebral artery myocyte showed that high-cholesterol diet did not down-regulate surface presence of BK protein. However, paxilline-induced cerebral artery constriction was diminished in arteries from rats on high-cholesterol diet. Conclusions: Our data indicate that dietary cholesterol protects against AICAC. This protection is caused by cholesterol buildup in the arterial tissue and diminished function (but not surface presence) of EtOH target-BK channel.

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