Faculty Collaboration Database

Overexpression of A(3) adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts. Am J Physiol Heart Circ Physiol 2002 Oct;283(4):H1562-8

Date

09/18/2002

Pubmed ID

12234810

Pubmed Central ID

PMC3934563

DOI

10.1152/ajpheart.00335.2002

Scopus ID

2-s2.0-0036783615 (requires institutional sign-in at Scopus site)   62 Citations

Abstract

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.

Author List

Cross HR, Murphy E, Black RG, Auchampach J, Steenbergen C

Author

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Energy Metabolism
Gene Expression
Heart Rate
Hydrogen-Ion Concentration
Magnetic Resonance Spectroscopy
Mice
Mice, Transgenic
Myocardial Contraction
Myocardial Ischemia
Myocardium
Phosphocreatine
Receptor, Adenosine A3
Receptors, Purinergic P1
Recovery of Function