Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume 41, Issue 4, Pages 562-570Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00005344-200304000-00008
Keywords
mouse coronary circulation; vasodilation; heart rate; adenosine A(2A) receptor; Adenosine A(2B) receptor
Funding
- NHLBI NIH HHS [HL-27339] Funding Source: Medline
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To clarify which adenosine receptor subtype(s) are responsible for regulation of coronary flow through endogenous adenosine, coronary vascular responses were examined in isolated hearts from wild-type (WT) and A(2A) knockout (A(2A)KO) mice. Adenosine deaminase inhibitor, erythro-9-hydroxy-nonyl-adenine (EHNA), and adenosine kinase inhibitor, iodotubericidine (ITU), were used to examine the effects of endogenous adenosine. Combined infusion of EHNA and ITU in Balb/c hearts produced comparable increases in coronary flow as exerted by exogenous adenosine while they markedly decreased the heart rate, and these effects were reversed by adenosine receptor antagonist, 8-p-sulfophenyl-theophylline (8-SPT). Similarly, EHNA and ITU increased coronary flow in WT hearts to 422% of baseline, whereas this response was reduced to 144% of baseline in A(2A)KO hearts. Heart rate was equally reduced (approximately 50% of baseline) in both groups. Alloxazine (A(2B) receptor antagonist) abolished EHNA- and ITU-induced coronary flow in A(2A)KO hearts without altering the reduced heart rate. Selective A, receptor antagonist, 8-cyclopentyl-1-1,3-dipropylxanthine (DPCPX), reversed EHNA- and ITU-induced decreases in heart rate without altering the elevated coronary flow. These findings suggest that coronary vascular responses to endogenous adenosine mimic those produced by exogenous adenosine and are mediated at least by activation of both A(2A) and A(2B) receptors in isolated mouse hearts.
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