心筋ならびに骨格筋虚血におけるノルエピネフリン放出機序の差異

抄録

Acute ischemia has been reported to deteriorate sympathetic outflow distal to the ischemic area. Although such deterioration was well observed in the myocardium, relative little is known about skeletal muscle. We investigated whether ischemia-induced norepinephrine (NE) release mechanism is different between myocardium and skeletal muscle. We implanted a microdialysis probe into the left ventricle and adductor muscle in the anesthetized cats and rabbits. Regional ischemia was introduced by occlusion of the main coronary artery, or by microspheres injection and ligation of common iliac artery. Dialysate NE levels were measured as an index of sympathetic nerve activity. The time courses of dialysate NE levels were examined with local administration of desipramine (DMI), w-conotoxin GVIA (CTX), TMB-8 (1 mM). Both ischemia increased dialysate NE levels from 107 ± 41 pg/ml at control to 19118 ± 5708 pg/ml at 60 min-coronary occlusion, and from 19 ± 4 pg/ml to 143 ± 30 pg/ml at 240 min-limb ischemia. Myocardial ischemia-induced NE level was suppressed by DMI (9347 ± 1768 pg/ml), but not by CTX or TMB-8. Limb ischemia-induced NE level was suppressed by TMB-8 (25 ± 5 pg/ml) but not by DMI or CTX. Ischemia induced NE release from myocardium and skeletal muscle. The myocardial ischemia-induced NE release attributes to the mechanisms of carrier mediated outward NE transport, while the limb ischemia-induced NE release attributes to the Ca²⁺ channel independent exocytosis via intracellular Ca²⁺ overload. [Jpn J Physiol 55 Suppl:S236 (2005)]