エンタカポンの心筋虚血に伴う心筋間質ノルエピネフリン動態に及ぼす影響

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Introduction: Catechol-O-methyltransferase (COMT) plays an important role for clearance of elevated catecholamine concentrations. Although experimental ischemic models clearly demonstrate marked accumulation of catecholamine in the heart, there are few reports on the physiological role of COMT activity for clearance of norepinephrine (NE) accumulation evoked by ischemia. We examined contribution of COMT to change in myocardial NE levels during myocardial ischemia and reperfusion. Methods: Acute myocardial ischemia was induced in anesthetized rabbits by a 60 min occlusion of the main coronary artery. We implanted a microdialysis probe into the left ventricular and measured myocardial interstitial NE and its metabolites levels in anesthetized rabbits. As an index of COMT activity, dialysate normetanephrine (NMN) levels were measured. We introduced myocardial ischemia by 60-min occlusion of the main coronary artery. The effects of entacapone (COMT inhibitor 10mg/kg, i.p.) on the ischemia-induced dialysate NE and NMN levels were examined. Results: Acute myocardial ischemia increased dialysate NE and NMN levels. Inhibition of COMT activity by entacapone augmented the ischemia-induced NE accumulation at 30-45 min of the coronary occlusion (vehicle: 27288 ± 7231, entacapone: 46146 ± 5979 pg/ml). Ischemia-induced NMN production was suppressed by entacapone (vehicle: 2023 ± 339, entacapone: 557 ± 136 pg/ml). Conclusion: In the ischemic heart, COMT activity contributes to removal of accumulated NE. [Jpn J Physiol 54 Suppl:S102 (2004)]