TY - JOUR
T1 - Endogenous adenosine increases coronary flow by activation of both A2A and A2B receptors in mice
AU - Talukder, M. A.Hassan
AU - Morrison, R. Ray
AU - Ledent, Catherine
AU - Mustafa, S. Jamal
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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 A2A knockout (A2AKO) mice. Adenosine deaminase inhibitor, erythro-9-hydroxy-nonyladenine (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 A2AKO hearts. Heart rate was equally reduced (approximately 50% of baseline) in both groups. Alloxazine (A2B receptor antagonist) abolished EHNA- and ITU-induced coronary flow in A2AKO hearts without altering the reduced heart rate. Selective A1 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 A2A and A2B receptors in isolated mouse hearts.
AB - 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 A2A knockout (A2AKO) mice. Adenosine deaminase inhibitor, erythro-9-hydroxy-nonyladenine (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 A2AKO hearts. Heart rate was equally reduced (approximately 50% of baseline) in both groups. Alloxazine (A2B receptor antagonist) abolished EHNA- and ITU-induced coronary flow in A2AKO hearts without altering the reduced heart rate. Selective A1 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 A2A and A2B receptors in isolated mouse hearts.
UR - http://www.scopus.com/inward/record.url?scp=0037379872&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037379872&partnerID=8YFLogxK
U2 - 10.1097/00005344-200304000-00008
DO - 10.1097/00005344-200304000-00008
M3 - Article
C2 - 12658057
AN - SCOPUS:0037379872
SN - 0160-2446
VL - 41
SP - 562
EP - 570
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 4
ER -