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Overexpression of A 3 adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts

2002; American Physical Society; Volume: 283; Issue: 4 Linguagem: Inglês

10.1152/ajpheart.00335.2002

1522-1539

H. R. Cross, Elizabeth Murphy, Richard G. Black, John A. Auchampach, Charles Steenbergen,

Advanced MRI Techniques and Applications

To determine whether A 3 adenosine receptor (A 3 AR) signaling modulates myocardial function, energetics, and cardioprotection, hearts from wild-type and A 3 AR-overexpressor mice were subjected to 20-min ischemia and 40-min reperfusion while 31 P NMR spectra were acquired. Basal heart rate and left ventricular developed pressure (LVDP) were lower in A 3 AR-overexpressor hearts than wild-type hearts. Ischemic ATP depletion was delayed and postischemic recoveries of contractile function, ATP, and phosphocreatine were greater in A 3 AR-hearts. To determine the role of depressed heart rate and to confirm A 3 AR-specific signaling, hearts were paced at 480 beats/min with or without 60 nmol/l MRS-1220 (A 3 AR-specific inhibitor) and then subjected to ischemia-reperfusion. LVDP was similar in paced A 3 AR-overexpressor and paced wild-type hearts. Differences in ischemic ATP depletion and postischemic contractile and energetic dysfunction remained in paced A 3 AR-overexpressor hearts versus paced wild-type hearts but were abolished by MRS-1220. In summary, A 3 AR overexpression decreased basal heart rate and contractility, preserved ischemic ATP, and decreased postischemic dysfunction. Pacing abolished the decreased contractility but not the ATP preservation or cardioprotection. Therefore, A 3 AR overexpression results in cardioprotection via a specific A 3 AR effect, possibly involving preservation of ATP during ischemia.