Role of A(2A) receptor in the modulation of myocardial reperfusion damage

Anna Cargnoni, Claudio Ceconi, Antonella Boraso, Palmira Bernocchi, Angela Monopoli, Salvatore Curello, Roberto Ferrari

Research output: Contribution to journalArticle

Abstract

Adenosine protects myocardium from ischemia and reperfusion damage; however, the mechanism of action is still under discussion. We investigated whether (a) adenosine protects isolated crystalloid-perfused rabbit heart from ischemia/reperfusion injury; (b) this action is receptor mediated and what receptor subtypes are involved, and (c) this action is dependent on an enhanced nitric oxide production. Our results showed a cardioprotective effect of adenosine (10-4 M), of nonselective adenosine-receptor agonist 5'-N-ethyl-carboxamidoadenosine (NECA; 5 x 10-6 M), and of A(2A) agonists CGS 21680 (10-8 and 10-6 M), 2-hexynylNECA (10-7 M). On the contrary, A1 agonist CCPA (10-8 and 10-6 M) does not provide any protection. The effect has been achieved in terms of significant reduction in contracture development during reperfusion [diastolic pressure was 46.8 ± 7.1 mm Hg (p <0.01); 46.1 ± 7.8 mm Hg (p <0.01); 46.9 ± 5.5 mm Hg (p <0.01); and 59.3 ± 6.7 mm Hg (p <0.05) with 10-4 M adenosine, 5 x 10-6 M NECA, 10-6 M CGS 21680, and 10-7 M 2-hexynylNECA, respectively, versus 77.6 ± 5.0 mm Hg in control]; reduced creatine phosphokinase release (13.5 ± 1.6, 22.2 ± 7.9, 14.2 ± 3.3, and 14.1 ± 4.5 U/gww in treated hearts vs. 34.6 ± 7.2 U/gww in controls; p <0.05); improved energy metabolism [adenosine triphosphate (ATP) content is 9.9 ± 0.5, 10.4 ± 0.6, 9.8 ± 0.5, and 10.5 ± 0.5 μmol/gdw in treated hearts vs. 7.6 ± 0.2 μmol/gdw; p <0.05]. Moreover, our data indirectly show a functional presence of A(2A) receptors on cardiomyocytes as the protection is A(2A) mediated and exerted only during reperfusion, although in the absence of blood and coronary flow changes. These activities appear independent of nitric oxide pathways, as adenosine and 2-hexynylNECA effects are not affected by the presence of a nitric oxide- synthase inhibitor (10-4 M L-NNA).

Original languageEnglish
Pages (from-to)883-893
Number of pages11
JournalJournal of Cardiovascular Pharmacology
Volume33
Issue number6
DOIs
Publication statusPublished - Jun 1999

Keywords

  • A(2A) agonists
  • Adenosine
  • Myocardial reperfusion damage

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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