HEMODYNAMIC-EFFECTS OF A SELECTIVE ADENOSINE A(2A) RECEPTOR AGONIST, CGS-21680, IN CHRONIC HEART-FAILURE IN ANESTHETIZED RATS

1 Recently we demonstrated that the administration of an AZA adenosine receptor agonist, CGS 21680, to anaesthetized rats with acute heart f ailure (1 h post-coronary artery ligation) resulted in an increase in cardiac output. In the present investigation, the effects of CGS 21680 on cardiac output, vascular resistance, heart rate, blood pressure an d mean circulatory filling pressure (Pmcf) were investigated in anaest hetized rats with chronic heart failure (8 weeks post-coronary artery ligation). 2 Experiments were conducted in five groups (n=6) of animal s: sham-operated vehicle-treated (0.9% NaCl; 0.037 mt kg(-1) min(-1)) animals in which the occluder was placed but not pulled to ligate the coronary artery; coronary artery-ligated vehicle-treated animals; and coronary artery-ligated CGS 21680-treated (0.1, 0.3 or 1.0 mu g kg(-1) min(-1)) animals. 3 Baseline blood pressure, cardiac output and rate of rise in left ventricular pressure (+ dP/dt) were significantly redu ced in animals with coronary artery ligation when compared to sham-ope rated animals. Coronary artery ligation resulted in a significant incr ease in left ventricular end-diastolic pressure, Pmcf and venous resis tance when compared to sham-operated animals. 4 Administration of CGS 21680 at 0.3 and 1.0 mu g kg(-1) min(-1) significantly (n=6; P<0.05) i ncreased cardiac output by 19+/-4% and 39+/-5%, and heart rate by 14+/ -2% and 15+/-1%, respectively, when compared to vehicle treatment in c oronary artery-ligated animals. Administration of CGS 21680 also signi ficantly reduced blood pressure and arterial resistance when compared to coronary artery-ligated vehicle-treated animals. Infusion of CGS 21 680 also significantly reduced venous resistance when compared to vehi cle-treated coronary artery-ligated animals. 5 The results show that h eart failure is characterized by reduced cardiac output, and increased left ventricular end-diastolic pressure, venous resistance and Pmcf. Acute treatment with CGS 21680 in animals with chronic heart failure d ecreased left ventricular end-diastolic pressure and increased cardiac output. This increase in cardiac output was the result of reduced art erial and venous resistances and increased heart rate.