一過性虚血時の冠血管トーヌス調節機構に関する研究―反応性充血に対するアデニレートサイクラーゼの関与―

Many lines of evidence suggest that adenosine partly regulates coronary vascular tone in response to myocardial ischemia after a brief coronary occlusion. However, the basic mechanisms of blood flow regulation of myocardial reactive hyperemia still remain unknown. This experiment was performed using the selective effect of forskolin to enhance the effects of agonists which exert receptor-mediated stimulation of adenylate cyclase. We exploited the potentiating effect of forskolin to test the hypothesis that activation of adenylate cyclase contributes to myocardial reactive hyperemia, especially by release of adenosine at the time of brief coronary occlusions. In ten open-chest dogs, intracoronary forskolin infusions, which produced plasma concentrations between 0.22 and 0.34 μM, slightly increased coronary blood flow and had no effect on hemodynamics or myocardial metabolism. Under these conditions, although peak reactive hyperemic flow rates were not affected, forskolin infusions reversibly increased repayments of flow debt significantly by 28, 25 and 27% following coronary occlusions of 15, 20 and 30 second, respectively (p<0.05). In other seven dogs, after observations of the effects of forskolin (0.16-0.26μM), 10μM of 8-phenyltheophylline, a potent adenosine antagonist, was intracoronarily infused simultaneously with forskolin. Forskolin potentiated debt repayments by about 23-27% following 15, 20 and 30 second occlusions. However, with simultaneous 8-phenyltheophylline, the effects of forskolin were eliminated significantly (p<0.05). The present results demonstrate that adenylate cyclase contributes to myocardial reactive hyperemia and adenosine has a significant role as metabolic regulator of reactive hyperemia through activation of adenylate cyclase.