Adenosine protects against angiotensin II-induced apoptosis in rat cardiocyte cultures

Adenosine has been found to be cardioprotective during episodes of cardiac ischemia/reperfusion through activation of the A(1) and possibly A(3) receptors. Therefore, we have investigated whether activation of these receptors can protect also against apoptotic death induced by angiotensin II (Ang II) in neonatal rat cardiomyocyte cultures. Exposure to Ang II (10 nM) resulted in a 3-fold increase in programmed cell death (p < 0.05). Pretreatment with the A(3) adenosine receptor agonist 2-chloro-N-6-cyclopentyladenosine (CCPA, 1 μM), abolished the effects of Ang II on programmed cardiomyocyte death. Moreover, exposure of cells to the A(1) adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) before pretreatment with CCPA, prevented the protective effect of the latter. Pretreatment with the A(3) adenosine receptor agonist N-6-(3-iodobenzyl) adenosine-5'-N-methyluronamide (IB-MECA, 0.1 μM), led to a partial decrease in apoptotic rate induced by Ang II. Exposure of myocytes to Ang II caused an immediate increase in the concentration of intracellular free Ca2+ that lasted 40-60 sec. Pretreatment of cells with CCPA or IB-MECA did not block Ang II-induced Ca2+ elevation. In conclusion, activation of adenosine A(1) receptors can protect the cardiac cells from apoptosis induced by Ang II, while activation of the adenosine A(3) receptors confers partial cardioprotection.