Cardioprotective Effects of Adenosine a 1 and a 2a Receptor Agonists in the Isolated Rat Heart
Authors: Lozza, G.; Conti, A.; Ongini, E.; Monopoli, A.
Source: Pharmacological Research, Volume 35, Number 1, January 1997 , pp. 57-64(8)
Publisher: Academic Press
Abstract:It has been postulated that the adenosine A 1 receptor subtype, but also A 2A receptors, are involved in mediating the beneficial properties of adenosine during ischemia and reperfusion. We investigated the effects of the selective A 1 adenosine receptor agonist, 2-chloro- N 6 -cyclopentyladenosine (CCPA), the selective A 2A adenosine receptor agonists, 2-[p-(2-carboxyethyl)phenetylamino]-5\'- N -ethylcarboxamidoadenosine (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. Global ischemia was induced for 15min in paced hearts followed by 60min reperfusion. Control hearts developed left ventricular dysfunction, as indicated by the increase in end diastolic pressure to 40.8±5.1 vs 5.9±1.0mmHg baseline, and in coronary perfusion pressure to 57.6±8.4 vs 28.8±2.2mmHg before ischemia. After 15min of reperfusion, ventricular function (LVDP) recovered by 83%, but creatine kinase levels were still significantly increased (294±55IUl -1 vs basal), indicating the occurrence of myocardial injury. All adenosine agonists added to the perfusion medium 15min prior to ischemia exerted protective effects against myocardial dysfunction and reperfusion injury. Thus, 2HE-NECA (100n M ), CGS 21680 (10n M ), CCPA (3n M ) and NECA (100n M ) significantly ( P <0.05) decreased end diastolic pressure by 50-75% as compared with the control group. Similarly, all compounds significantly ( P <0.05) reduced coronary perfusion pressure by 30-45% vs control. For all drugs, recovery of LVDP occurred immediately after restoration of coronary flow. At 15-min reperfusion the adenosine agonists decreased 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 reperfusion in isolated rat heart, even if through different mechanisms.
Document Type: Research Article
Affiliations: Schering-Plough Research Institute, San Raffaele Science Park, Via Olgettina 58, 20132 Milan, Italy
Publication date: January 1997