Document Detail


Altered mechanism of adenosine-induced coronary arteriolar dilation in early-stage metabolic syndrome.
MedLine Citation:
PMID:  19307464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Onset of the combined metabolic syndrome (MetS) is a complex progressive process involving numerous cardiovascular risk factors. Although patients with established MetS exhibit reduced coronary flow reserve and individual components of the MetS reduce microvascular vasodilation, little is known concerning the impact of early-stage MetS on the mechanisms of coronary flow control. Therefore, we tested the hypothesis that coronary arteriolar dilation to adenosine is attenuated in early-stage MetS by reduced A2 receptor function and diminished K+ channel involvement. Pigs were fed control or high-fat/cholesterol diet for 9 weeks to induce early-stage MetS. Coronary atheroma was determined in vivo with intravascular ultrasound. In vivo coronary dilation was determined by intracoronary adenosine infusion. Further, apical coronary arterioles were isolated, cannulated and pressurized to 60 cmH2O for in vitro pharmacologic assessment of adenosine dilation. Coronary atheroma was not different between groups, indicating early-stage MetS. Coronary arteriolar dilation to adenosine (in vivo) and 2-chloroadenosine (2-CAD; in vitro) was similar between groups. In control arterioles, 2-CAD-mediated dilation was reduced only by selective A(2A) receptor inhibition, whereas only dual A(2A/2B) inhibition reduced this response in MetS arterioles. Arteriolar A(2B), but not A(2A), receptor protein expression was reduced by MetS. Blockade of voltage-dependent K+ (K(v)) channels reduced arteriolar sensitivity to 2-CAD in both groups, whereas ATP-sensitive K+ (K(ATP)) channel inhibition reduced sensitivity only in control arterioles. Our data indicate that the mechanisms mediating coronary arteriolar dilation to adenosine are altered in early-stage MetS prior to overt decrements in coronary vasodilator reserve.
Authors:
Shawn B Bender; Johnathan D Tune; Lena Borbouse; Xin Long; Michael Sturek; M Harold Laughlin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-23
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  234     ISSN:  1535-3702     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-29     Completed Date:  2009-07-14     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  683-92     Citation Subset:  IM    
Affiliation:
E102 Vet Med Bldg, Dept. of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA. benders@missouri.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine / pharmacology*
Adenosine A2 Receptor Agonists
Animals
Arterioles / metabolism,  physiopathology
Cardiovascular Diseases / etiology,  metabolism,  physiopathology
Cholesterol / pharmacology
Coronary Circulation / drug effects*
Dietary Fats / pharmacology
Male
Metabolic Syndrome X / complications,  metabolism*,  physiopathology
Potassium Channels, Voltage-Gated / antagonists & inhibitors,  metabolism
Receptor, Adenosine A2A / metabolism
Risk Factors
Swine
Swine, Miniature
Vasodilation / drug effects*
Vasodilator Agents / pharmacology*
Grant Support
ID/Acronym/Agency:
AR-048523/AR/NIAMS NIH HHS; HL-062552/HL/NHLBI NIH HHS; HL-52490/HL/NHLBI NIH HHS; R01 HL062552-09A2/HL/NHLBI NIH HHS; R01 HL062552-10/HL/NHLBI NIH HHS; RR-013223/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Adenosine A2 Receptor Agonists; 0/Dietary Fats; 0/Potassium Channels, Voltage-Gated; 0/Receptor, Adenosine A2A; 0/Vasodilator Agents; 57-88-5/Cholesterol; 58-61-7/Adenosine
Comments/Corrections

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