These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A(2A) adenosine receptor-mediated increase in coronary flow in hyperlipidemic APOE-knockout mice.
    Author: Teng B, Mustafa SJ.
    Journal: J Exp Pharmacol; 2011 Jul; 2011(3):59-68. PubMed ID: 21847356.
    Abstract:
    Adenosine-induced coronary vasodilation is predominantly A(2A) adenosine receptor (AR)-mediated, whereas A(1) 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)-knockout mice, CF responses to nonspecific adenosine agonist (5'-N-ethylcarboxamide adenosine, NECA) and specific adenosine agonists (2-chloro-N6-cyclopentyl-adenosine [CCPA, A(1) AR-specific] and CGS-21680, A(2A) 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 ± 3.58), APOE (13.22 ± 2.78), and APOE on high-fat diet (HFD) for 12 weeks (APOE-HFD, 12.37 ± 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 A(2A) 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 A(2A) AR in the aorta from APOE and APOE-HFD. This study provides the first evidence that CF responses to A(2A) AR stimulation were upregulated in hyperlipidemic/atherosclerotic animals. The speculation is that the use of A(2A) AR-specific agonist for myocardial perfusion imaging (such as regadenoson) could overestimate the coronary reserve in coronary artery disease patients.
    [Abstract] [Full Text] [Related] [New Search]