Role of Adenosine Receptor Activation in Antioxidant Enzyme Regulation During Ischemia–Reperfusion in the Isolated Rat Heart

Abstract

The aim of the present study was to investigate the protective role of pharmacological preconditioning on antioxidant enzymes using A(1) and A(3) adenosine receptor agonists in the recovery of the isolated myocardium after cardioplegic ischemia. Two different modes of preconditioning were studied: isolated rat hearts were perfused with A(1) receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) or A(3) 2-chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (Cl-IB-MECA) (1 nM), followed by cardioplegic ischemia and reperfusion (30 min each) (perfusion mode), or CCPA or Cl-IB-MECA (100 micro g/kg) were injected intravenously 24 h before the experiment (injection mode). Hearts treated with CCPA improved in terms of mechanical function, infarct size, ATP levels, superoxide dismutase, and catalase (p < 0.005) in both modes of administration. Cl-IB-MECA was beneficial mainly in the injected group. Reduced damage to the mitochondria in the CCPA-treated hearts was observed using electron microscopy evaluation. In the Cl-IB-MECA-injected hearts, mitochondrial damage was moderate. CCPA in both modes of treatment and Cl-IB-MECA in the injected mode were beneficial in protecting the perfused isolated rat heart, subjected to normothermic cardioplegic ischemia. This protection was partially related to the higher myocardial activity of superoxide dismutase and catalase.

Local delivery of a PKCε-activating peptide limits ischemia reperfusion injury in the aged female rat heart

“…Also, the SODmimetic EUK-8 was cardioprotective in isolated hearts from adult OVX female rats (47). Perhaps of greatest interest is the report of increased SOD activity following pharmacological preconditioning with the adenosine A 1 receptor agonist CCPA in isolated rat hearts (15), since PKCε is known to be activated downstream of the A 1 receptor (11). It is likely that increases in GPX and SOD2 immediately following PKCε activation may serve to combat increased reactive oxygen species production in the aged female heart (29).…”

Effect of adenosine A2A receptor agonist (CGS) on ischemia/reperfusion injury in isolated rat liver

“…33 Our group previously reported on the protective role of pharmacological preconditioning with A1 and A3 adenosine receptor agonists in I/R-induced injury in the isolated rat heart. 34 The use of selective adenosine A2A receptor agonists for pharmacologic hepatic preconditioning in humans is supported by the successful application of adenosine for myocardial protection during coronary angioplasty. 35 Recently, Yadav et al, 36 using the TUNEL assay and measurements of intrahepatic caspase-3 activity, found that ischemic preconditioning in mouse liver confers dramatic protection against prolonged ischemia by inhibiting apoptosis through downregulation of caspase-3 activity.…”

Anti-ischemic effects of multivalent dendrimeric A3 adenosine receptor agonists in cultured cardiomyocytes and in the isolated rat heart

“…A fluid-filled latex balloon was inserted via the left atrium into the left ventricle and inflated to set a left-ventricular end-diastolic pressure (LVEDP) between 5–10 mmHg. Coronary flow was collected every 10 min, left ventricular developed pressure (LVP) was continuously recorded and the derivatives ±dP/dt max were calculated by the CODAS data acquisition system (San Diego, CA, USA) [13]. Hearts were excluded from further data analysis as a result of one of the following undesirable situations: 1.…”

“…Activation of this receptor preconditions cardiomyocytes in culture, in isolated hearts, and in vivo protects against the damaging effects of ischemia/reperfusion injury. A 3 AR agonists are attractive as cardioprotective agents because they do not alter systemic hemodynamic parameters in non-rodent species and are effective upon preischemic administration or only during reperfusion [8–13]. The prototypical A 3 AR agonists N 6 -(3-iodobenzyl)-adenosine-5′- N -methylcarboxamide (IB-MECA) and its 2-chloro derivative Cl-IB-MECA have been tested in experimental animal models of ischemia/reperfusion injury [14,15].…”