CARDIOPROTECTIVE EFFECTS OF ADENOSINE A(1) AND A(2A) RECEPTOR AGONISTS IN THE ISOLATED RAT-HEART

It has been postulated that the adenosine Al receptor subtype, but als o A(2A) receptors, are involved in mediating the beneficial properties of adenosine during ischemia and reperfusion. We investigated the eff ects of the selective A(1) adenosine receptor agonist, 2-chloro-N-6-cy clopentyladenosine (CCPA), the selective A(2A) adenosine receptor agon ists, 2-[p-(2-carboxyethyl)phenetylamino] -5'-N-ethylcarboxamidoadenos ine (CGS 21680), 2-hexynyl-5'-N-ethyl-carboxamidoadenosine (2HE-NECA), and the non selective agonist, 5'-N-ethyl-carboxamidoadenosine (NECA) , on ischemia-reperfusion injury in Langendorff-perfused rat hearts. G lobal ischemia was induced for 15 min in paced hearts followed by 60 m in reperfusion. Control hearts developed left ventricular dysfunction, as indicated by the increase in end diastolic pressure to 40.8+/-5.1 vs 5.9+/-1.0 mm Hg baseline, and in coronary perfusion pressure to 57. 6+/-8.4 vs 28.8+/-2.2 mm Hg before ischemia. After 15 min of reperfusi on, ventricular function (LVDP) recovered by 83%, but creatine kinase levels were still significantly increased (294+/-55 IUl(-1) vs basal), indicating the occurrence of myocardial injury. All adenosine agonist s added to the perfusion medium 15 min prior to ischemia exerted prote ctive effects against myocardial dysfunction and reperfusion injury. T hus, 2HE-NECA (100 nM), CGS 21680 (10 nM), CCPA (3 nM) and NECA (100 n M) significantly (P<0.05) decreased end diastolic pressure by 50-75% a s compared with the control group. Similarly, all compounds significan tly (P<0.05) reduced coronary perfusion pressure by 30-45% vs control. For all drugs, recovery of LVDP occurred immediately after restoratio n of coronary flow. At 15-min reperfusion the adenosine agonists decre ased myocardial creatine kinase release by 80-95% (P<0.05 vs control). These findings indicate that both A(1) and A(2A) adenosine receptors are involved in protecting the myocardium against ischemia and reperfu sion in isolated rat heart, even if through different mechanisms. (C) 1997 The Italian Pharmacological Society.