Source:http://linkedlifedata.com/resource/pubmed/id/11306529
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
2001-4-18
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pubmed:abstractText |
BACKGROUND: Flow-induced vasodilation (FID) is a physiological mechanism for regulating coronary flow and is mediated largely by nitric oxide (NO) in animals. Because hyperpolarizing mechanisms may play a greater role than NO in the microcirculation, we hypothesized that hyperpolarization contributes importantly to FID of human coronary arterioles. METHODS AND RESULTS: Arterioles from atria or ventricles were cannulated for videomicroscopy. Membrane potential of vascular smooth muscle cells (VSMCs) was measured simultaneously. After constriction with endothelin-1, increases in flow induced an endothelium-dependent vasodilation. Nomega-Nitro-L-arginine methyl ester 10(-4) mol/L modestly impaired FID of arterioles from patients without coronary artery disease (CAD), whereas no inhibition was seen in arterioles from patients with CAD. Indomethacin 10(-5) mol/L was without effect, but 40 mmol/L KCl attenuated maximal FID. Tetraethylammonium 10(-3) mol/L but not glibenclamide 10(-6) mol/L reduced FID. Charybdotoxin 10(-8) mol/L impaired both FID (15+/-3% versus 75+/-12%, P<0.05) and hyperpolarization (-32+/-2 mV [from -28+/-2 mV after endothelin-1] versus -42+/-2 mV [-27+/-2 mV], P<0.05). Miconazole 10(-6) mol/L or 17-octadecynoic acid 10(-5) mol/L reduced FID. By multivariate analysis, age was an independent predictor for the reduced FID. Conclusions-We conclude that shear stress induces endothelium-dependent vasodilation, hyperpolarizing VSMCs through opening Ca(2+)-activated K(+) channels in human coronary arterioles. In subjects without CAD, NO contributes to FID. NO and prostaglandins play no role in patients with CAD; rather, cytochrome P450 metabolites are involved. This is consistent with a role for endothelium-derived hyperpolarizing factor in FID of the human coronary microcirculation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/17-octadecynoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Charybdotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/Glyburide,
http://linkedlifedata.com/resource/pubmed/chemical/Miconazole,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Tetraethylammonium
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1524-4539
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
17
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1992-8
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:11306529-Age Factors,
pubmed-meshheading:11306529-Arterioles,
pubmed-meshheading:11306529-Blood Flow Velocity,
pubmed-meshheading:11306529-Calcium,
pubmed-meshheading:11306529-Charybdotoxin,
pubmed-meshheading:11306529-Coronary Vessels,
pubmed-meshheading:11306529-Endothelin-1,
pubmed-meshheading:11306529-Enzyme Inhibitors,
pubmed-meshheading:11306529-Fatty Acids, Unsaturated,
pubmed-meshheading:11306529-Female,
pubmed-meshheading:11306529-Glyburide,
pubmed-meshheading:11306529-Humans,
pubmed-meshheading:11306529-Male,
pubmed-meshheading:11306529-Membrane Potentials,
pubmed-meshheading:11306529-Miconazole,
pubmed-meshheading:11306529-Middle Aged,
pubmed-meshheading:11306529-Multivariate Analysis,
pubmed-meshheading:11306529-Potassium Channel Blockers,
pubmed-meshheading:11306529-Potassium Channels,
pubmed-meshheading:11306529-Potassium Chloride,
pubmed-meshheading:11306529-Stress, Mechanical,
pubmed-meshheading:11306529-Tetraethylammonium,
pubmed-meshheading:11306529-Vasodilation
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pubmed:year |
2001
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pubmed:articleTitle |
Flow-induced dilation of human coronary arterioles: important role of Ca(2+)-activated K(+) channels.
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pubmed:affiliation |
VA Medical Center, the Department of Medicine, and the Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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