Selective deletion of the A1 adenosine receptor abolishes heart-rate slowing effects of intravascular adenosine in vivo.
OBJECTIVE
Intravenous adenosine induces temporary bradycardia. This is due to the activation of extracellular adenosine receptors (ARs). While adenosine can signal through any of four ARs (A1AR, A2AAR, A2BAR, A3AR), previous ex vivo studies implicated the A1AR in the heart-rate slowing effects. Here, we used comparative genetic in vivo studies to address the contribution of individual ARs to the heart-rate slowing effects of intravascular adenosine.


RESULTS
We studied gene-targeted mice for individual ARs to define their in vivo contribution to the heart-rate slowing effects of adenosine. Anesthetized mice were treated with a bolus of intravascular adenosine, followed by measurements of heart-rate and blood pressure via a carotid artery catheter. These studies demonstrated dose-dependent slowing of the heart rate with adenosine treatment in wild-type, A2AAR(-/-), A2BAR(-/-), or A3AR(-/-) mice. In contrast, adenosine-dependent slowing of the heart-rate was completely abolished in A1AR(-/-) mice. Moreover, pre-treatment with a specific A1AR antagonist (DPCPX) attenuated the heart-rate slowing effects of adenosine in wild-type, A2AAR(-/-), or A2BAR(-/-) mice, but did not alter hemodynamic responses of A1AR(-/-) mice.


CONCLUSIONS
The present studies combine pharmacological and genetic in vivo evidence for a selective role of the A1AR in slowing the heart rate during adenosine bolus injection.
Koeppen
Michael
M
Mucosal Inflammation Program, Department of Anesthesiology and Perioperative Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Eckle
Tobias
T
Eltzschig
Holger K
HK
D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D043682:Receptor, Adenosine A1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine
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