α1-Adrenoceptor activity regulates release of adenosine from the ischemic myocardium in dogs

Abstract

The goal of this study was to test the hypothesis that α1-adrenoceptor activity plays a key role in the release of adenosine from the ischemic myocardium. In 51 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery, and adenosine release into the local coronary vein was measured by the radioimmunoassay technique following the reduction of perfusion pressure for 20 minutes under α1-, α2-, and β-adrenoceptor attenuations. Adenosine and lactate concentrations in the coronary arterial and venous blood sampled from the perfused area were determined, as well as fractional shortening. In the untreated condition, adenosine release was significantly (p < 0.01) increased from 1.7 ± 0.8 (SEM) to 8.8 ± 1.3 nmol/100 g/min, 20 minutes after the onset of hypoperfusion (coronary blood flow: 28 ± 2 ml/100 g/min) following the initial overshoot release. Neither β- nor α2-adrenoceptor attenuation affected the increase in adenosine release during hypoperfusion except for the slight attenuation of the overshoot release by β-attenuation. In contrast, intracoronary infusions of prazosin and phentolamine during coronary hyperfusion markedly attenuated (p < 0.01) release of adenosine (1.8 ± 0.7 nmol/100 g/min at 20 minutes). The extents of decreases in fractional shortening and lactate production were comparable between the untreated and α1-adrenoceptor attenuation. Moreover, when prazosin was administered into the coronary artery during a steady-state of hypoperfusion, adenosine release was significantly (p < 0.01) decreased and a further decrease in coronary flow was observed. In 19 other dogs, we tested whether hyperemic coronary flow due to endogenous adenosine was reduced by α1-attenuation. Hyperemic flow was produced by intracoronary embolization of microspheres (15 μm) or transient occlusion of a coronary artery. In both protocols hyperemic flow was significantly reduced by α1-attenuation associated with a marked reduction of adenosine release. These results indicate that α1-adrenoceptor attenuation reduces the adenosine release from the ischemic myocardium, and thus reduces the ischemia-induced hyperemic flow. Thus we concluded that α1-adrenoceptor activity largely contributes to the mechanism whereby adenosine is released from the ischemic myocardium.