Release of noradrenaline in myocardial ischemia--importance of local inactivation by neuronal and extraneuronal mechanisms.
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.
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
D008333:Mandelic Acids; D009647:Normetanephrine; D008734:Methoxyhydroxyphenylglycol; C000989:3,4-dihydroxymandelic acid; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D003345:Corticosterone; D009638:Norepinephrine