title: Release of noradrenaline in myocardial ischemia--importance of local inactivation by neuronal and extraneuronal mechanisms.
abstract: The mechanisms responsible for the local inactivation of noradrenaline (NA) released during myocardial ischemia were examined in the isolated perfused rat heart preloaded with 3H-NA. Two different types of ischemia were used: (a) 90% global flow reduction (global ischemia), and (b) ligation of the left coronary artery (regional ischemia). The coronary effluent was collected at different intervals during ischemia and reperfusion, and 3H-NA was separated from its tritiated metabolites using HPLC. During ischemia, a gradual increase in the efflux of 3H-NA was observed, which was accompanied by a shift from predominantly neuronal metabolism towards increased efflux of extraneuronally formed metabolites. During the first minute of reperfusion, the metabolic pattern of 3H-NA was not substantially changed as compared with that observed immediately before reperfusion, indicating a wash-out of 3H-NA and its tritiated metabolites accumulated in the tissue during the ischemic period. Addition of corticosterone to the perfusion medium (to inhibit extraneuronal uptake of 3H-NA) was associated with an increased efflux of 3H-NA during the ischemic period. In contrast, addition of the neuronal uptake blocker desipramine caused a decreased efflux of 3H-NA during ischemia. In conclusion, these experiments demonstrate an ischemia-induced release of myocardial NA, in all probability due to the recently proposed carrier-mediated efflux mechanism. The release is parallelled by an increasing extraneuronal inactivation of released transmitter.
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D003345:Corticosterone / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D008297:Male; D008333:Mandelic Acids / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008333:Mandelic Acids; D009647:Normetanephrine; D008734:Methoxyhydroxyphenylglycol; C000989:3,4-dihydroxymandelic acid; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D003345:Corticosterone; D009638:Norepinephrine