Intrinsic activation of A1 adenosine receptors during ischemia and repurfusion improves ischemic tolerance

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Title Intrinsic activation of A1 adenosine receptors during ischemia and repurfusion improves ischemic tolerance
Author Peart, Jason Nigel John; Headrick, John Patrick
Journal Name American Journal of Physiology: Heart and Circulatory Physiology
Year Published 2000
Place of publication USA
Publisher American Physiological Society
Abstract We assessed the role of A1 adenosine receptor (A1AR) activation by endogenous adenosine in the modulation of ischemic contracture and postischemic recovery in Langendorff-perfused mouse hearts subjected to 20 min of total ischemia and 30 min of reperfusion. In control hearts, the rate-pressure product (RPP) and first derivative of pressure development over time (+dP/dt) recovered to 57 ± 3 and 58 ± 3% of preischemia, respectively. Diastolic pressure remained elevated at 20 ± 2 mmHg (compared with 3 ± 1 mmHg preischemia). Interstitial adenosine, assessed by microdialysis, rose from ∼0.3 to 1.9 μM during ischemia compared with ∼15 μM in rat heart. Nonetheless, these levels will near maximally activate A1ARs on the basis of effects of exogenous adenosine and 2-chloroadenosine. Neither A1AR blockade with 200 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) during the ischemic period alone nor A1AR activation with 50 nMN 6-cyclopentyladenosine altered rapidity or extent of ischemic contracture. However, ischemic DPCPX treatment significantly depressed postischemic recovery of RPP and +dP/dt (44 ± 3 and 40 ± 4% of preischemia, respectively). DPCPX treatment during the reperfusion period alone also reduced recovery of RPP and +dP/dt (to 44 ± 2 and 47 ± 2% of preischemia, respectively). These data indicate that1) interstitial adenosine is lower in mouse versus rat myocardium during ischemia, 2) A1AR activation by endogenous adenosine or exogenous agonists does not modify ischemic contracture in murine myocardium, 3) A1AR activation by endogenous adenosine during ischemia attenuates postischemic stunning, and 4) A1AR activation by endogenous adenosine during the reperfusion period also improves postischemic contractile recovery.
Peer Reviewed Yes
Published Yes
Publisher URI http://ajpheart.physiology.org/content/279/5/H2166
Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
Volume 279
Page from H2166
Page to H2175
ISSN 0363-6135
Date Accessioned 2001-01-01
Date Available 2015-02-05T03:44:04Z
Language en_US
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Subject PRE2009-Medical & Health Sciences
URI http://hdl.handle.net/10072/3467
Publication Type Article in Scholarly Refereed Journal
Publication Type Code c1

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