%0 Journal Article
%T A2A adenosine receptor-mediated increase in coronary flow in hyperlipidemic APOE¨Cknockout mice
%A Teng B
%A Mustafa SJ
%J Journal of Experimental Pharmacology
%D 2011
%I Dove Medical Press
%R http://dx.doi.org/10.2147/JEP.S18945
%X 2A adenosine receptor-mediated increase in coronary flow in hyperlipidemic APOE¨Cknockout mice Original Research (1960) Total Article Views Authors: Teng B, Mustafa SJ Published Date July 2011 Volume 2011:3 Pages 59 - 68 DOI: http://dx.doi.org/10.2147/JEP.S18945 Bunyen Teng, S Jamal Mustafa Department of Physiology and Pharmacology and Center for Cardiovascular and Respiratory Sciences, West Virginia University, Morgantown, WV, USA Abstract: Adenosine-induced coronary vasodilation is predominantly A2A adenosine receptor (AR)-mediated, whereas A1 AR is known to negatively modulate the coronary flow (CF). However, the coronary responses to adenosine in hyperlipidemia and atherosclerosis are not well understood. Using hyperlipidemic/atherosclerotic apolipoprotein E (APOE)¨Cknockout mice, CF responses to nonspecific adenosine agonist (5'-N-ethylcarboxamide adenosine, NECA) and specific adenosine agonists (2-chloro-N6-cyclopentyl-adenosine [CCPA, A1 AR-specific] and CGS-21680, A2A AR-specific) were assessed using isolated Langendorff hearts. Western blot analysis was performed in the aorta from APOE and their wild-type (WT) control (C57BL/6J). Baseline CF (expressed as mL/min/g heart weight) was not different among WT (13.23 ¡À 3.58), APOE (13.22 ¡À 2.78), and APOE on high-fat diet (HFD) for 12 weeks (APOE-HFD, 12.37 ¡À 4.76). Concentration response curves induced by CGS-21680 were significantly shifted to the left in APOE and APOE-HFD when compared with WT. CCPA induced an increase in CF only at 10-6 M in all groups and the effect was reversed by the addition of a selective A2A AR antagonist, SCH-58261 (10-6 M), and a significant decrease in CF from baseline was observed. Western blot analysis showed a significant upregulation of A2A AR in the aorta from APOE and APOE-HFD. This study provides the first evidence that CF responses to A2A AR stimulation were upregulated in hyperlipidemic/atherosclerotic animals. The speculation is that the use of A2A AR-specific agonist for myocardial perfusion imaging (such as regadenoson) could overestimate the coronary reserve in coronary artery disease patients.
%K hyperlipidemia
%K atherosclerosis
%K apolipoprotein E¨Cknockout mice
%K coronary flow regulation
%K A2A adenosine receptor
%U https://www.dovepress.com/a2a-adenosine-receptor-mediated-increase-in-coronary-flow-in-hyperlipi-peer-reviewed-article-JEP