A crucial role of ongoing anaerobic glycolysis in attenuating acute ischemia-induced release of myocardial noradrenaline.
The myocardial energy requirements of the noradrenergic nerve terminal to retain its transmitter during acute myocardial ischemia were examined in the isolated perfused rat heart. In hearts perfused with glucose as exogenous substrate no increased release of noradrenaline (NA) could be detected during ischemia. In contrast, an increased efflux of NA was seen from glucose-perfused hearts when the glycolytic pathway was inhibited with 0.5 mM iodacetic acid. Accordingly, induction of ischemia in glycogen-depleted hearts (in the absence of exogenous substrate) or in hearts perfused with either lactate, pyruvate or acetate was also associated with a marked efflux of NA. However, no efflux was detected from glycogen-depleted hearts when glucose was present during the ischemic period. Uncoupling of oxidative metabolism with 0.1 mM 2.4-dinitrophenol did not cause any increased loss of NA during ischemia. In conclusion, these results demonstrate that severe restriction in coronary flow is accompanied by increased release of myocardial NA. Furthermore, maintainance of anaerobic glycolysis is of crucial importance for retention of the noradrenergic transmitter during ischemic conditions.
Carlsson
L
L
Department of Pharmacology, University of Göteborg, Sweden.
D019297:2,4-Dinitrophenol; D000693:Anaerobiosis; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D004140:Dinitrophenols / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D004140:Dinitrophenols; D007461:Iodoacetates; D006003:Glycogen; D019297:2,4-Dinitrophenol; D019807:Iodoacetic Acid; D009638:Norepinephrine