Species-dependent hemodynamic effects of adenosine A(3)-receptor agonists IB-MECA and Cl-IB-MECA

Species-dependent hemodynamic effects of adenosine As-receptor agonists IB- MECA and Cl-IB-MECA. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H2076-H 2084, 1999.-The purpose of this study was to compare the hemodynamic effect s of the adenosine AB-receptor agonists N-6-(3-iodobenzyl)-9-[5-(methylcarb amoyl)-beta-D-ribofuranosyl]adenine (IB-MECA) and 2-chloro-N-6-(3-iodobenzy l)-9-[5-(methylcarbamoyl)-beta-D-ribofuranosyl]aden (Cl-IB-MECA) in isolate d rat and rabbit hearts and in the intact, open-chest pig. Isolated hearts perfused with Krebs-Henseleit buffer at a constant pressure (70 mmHg) were treated with 50 nM of either IB-MECA or Cl-IB-MECA. Neither IB-MECA nor Cl- IB-NIECA altered ventricular function or heart rate in the isolated rat and rabbit hearts, and neither agent altered coronary flow in the rabbit. Howe ver, 2 min of IB-MECA treatment in the isolated rat heart increased coronar y flow by 25%, an effect that did not exhibit tachyphylaxis. The IB-MECA-in duced coronary dilation was only partially attenuated by the adenosine A(3) -receptor antagonist MRS-1191 (50 nM). IB-MECA-induced coronary dilation wa s completely blocked by the adenosine Ag,-receptor antagonist 7-(2-phenylet hyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine(S ch-58261, 50 nM). Cl-IB-MECA (50 nM) did not increase coronary flow in the rat, but 100 nM did increase flow by 18%. In pentobarbital sodium-anestheti zed pigs IB-MECA(5 mu g/kg iv) decreased systemic blood pressure and increa sed pulmonary artery pressure, effects that did exhibit tachyphylaxis. Thes e results illustrate that adenosine A(3)-receptor agonists produce species- dependent effects, which in the rat heart appear to be caused by adenosine A(2a)-receptor activation.