Journal
PLOS ONE
Volume 4, Issue 8, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0006784
Keywords
-
Categories
Funding
- NHLBI NIH HHS [R01 HL092188, R01-HL092188] Funding Source: Medline
Ask authors/readers for more resources
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. Methods and 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available