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Am J Physiol Heart Circ Physiol (June 20, 2002). doi:10.1152/ajpheart.00335.2002
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Articles in PresS, published online ahead of print June 20, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00335.2002
Submitted on April 15, 2002
Accepted on June 17, 2002

Overexpression of the A3 Adenosine Receptor Decreases Heart Rate, Preserves Energetics and Protects the Ischemic Heart

Heather R. Cross1*, Elizabeth Murphy2, Richard G. Black3, John Auchampach3, and Charles Steenbergen1

1 Department of Pathology, Duke University Medical Center, Durham, NC, USA
2 Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
3 Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA

* To whom correspondence should be addressed. E-mail: cross017{at}mc.duke.edu.

To determine whether A3-adenosine receptor (A3AR) signaling modulates myocardial function, energetics and cardioprotection, hearts from wild-type and A3AR-overexpressor mice were subjected to 20 min ischemia/40 min reperfusion while 31P NMR spectra were acquired. Basal heart rate and developed pressure (LVDP) were lower in A3AR-overexpressor hearts than wild-type. Ischemic ATP depletion was delayed and post-ischemic recoveries of contractile function, ATP and PCr were greater in A3AR-hearts. To determine the role of depressed heart rate and confirm A3AR-specific signaling, hearts were paced at 480 bpm ± 60 nmol/L MRS-1220 (A3AR-specific inhibitor) then subjected to ischemia/reperfusion. LVDP was similar in paced-A3AR vs. paced wild-type hearts. Differences in ischemic ATP depletion and post-ischemic contractile and energetic dysfunction remained in paced A3AR-overexpressor hearts vs. paced wild-type but were abolished by MRS-1220. In summary, A3AR-overexpression decreased basal heart rate and contractility, preserved ischemic ATP and decreased post-ischemic dysfunction. Pacing abolished the decreased contractility but not the ATP preservation or cardioprotection. Therefore, A3AR-overexpression results in cardioprotection via a specific A3AR-effect, possibly involving preservation of ATP during ischemia.




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