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 A1 and possibly A1 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 A1 adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 1 microM), abolished the effects of Ang II on programmed cardiomyocyte death. Moreover, exposure of cells to the A1 adenosine receptor antagonist 8-cyclopentyl- 1,3-dipropylxanthine (CPX) before pretreatment with CCPA, prevented the protective effect of the latter. Pretreatment with the A3 adenosine receptor agonist N6-(3-iodobenzyl) adenosine-5'-N-methyluronamide (IB-MECA, 0.1 microM), 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 A1 receptors can protect the cardiac cells from apoptosis induced by Ang II, while activation of the adenosine A3 receptors confers partial cardioprotection.