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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. Her...

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Autores principales: Koeppen, Michael, Eckle, Tobias, Eltzschig, Holger K.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727950/
https://www.ncbi.nlm.nih.gov/pubmed/19707555
http://dx.doi.org/10.1371/journal.pone.0006784
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author Koeppen, Michael
Eckle, Tobias
Eltzschig, Holger K.
author_facet Koeppen, Michael
Eckle, Tobias
Eltzschig, Holger K.
author_sort Koeppen, Michael
collection PubMed
description 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.
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spelling pubmed-27279502009-08-26 Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo Koeppen, Michael Eckle, Tobias Eltzschig, Holger K. PLoS One Research Article 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. Public Library of Science 2009-08-26 /pmc/articles/PMC2727950/ /pubmed/19707555 http://dx.doi.org/10.1371/journal.pone.0006784 Text en Koeppen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Koeppen, Michael
Eckle, Tobias
Eltzschig, Holger K.
Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo
title Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo
title_full Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo
title_fullStr Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo
title_full_unstemmed Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo
title_short Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo
title_sort selective deletion of the a1 adenosine receptor abolishes heart-rate slowing effects of intravascular adenosine in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727950/
https://www.ncbi.nlm.nih.gov/pubmed/19707555
http://dx.doi.org/10.1371/journal.pone.0006784
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