Paradoxical role of neuronal uptake for the locally mediated release of endogenous noradrenaline in the ischemic myocardium.
The accumulation of endogenous noradrenaline within the extracellular space of the ischemic myocardium was studied in the isolated perfused (Langendorff) rat heart. The hearts were subjected to various periods of ischemia, and the noradrenaline overflow that occurred during the ensuing period of reperfusion was estimated radioenzymatically. Ischemic periods of less than 10 min are not associated with an increased overflow of noradrenaline during reperfusion. Longer periods are accompanied by an overflow, increasing with lengthening of the preceding ischemia to 1,270 +/- 48 pmol/g heart after 60 min of ischemia, as compared with 3.7 +/- 0.6 pmol/g during control perfusion. The kinetics of noradrenaline overflow suggest that the noradrenaline detected during reperfusion is released from the sympathetic neurons predominantly during ischemia and is then washed out from the extracellular space. The noradrenaline overflow induced by ischemia is not influenced by the lack of extracellular calcium. Blockade of neuronal uptake reduces noradrenaline overflow after ischemic periods of between 10 and 40 min (at 30 min from 481 +/- 56 to 91 +/- 12 pmol/g heart). The noradrenaline overflow after longer periods of ischemia is not affected by blockade of neuronal uptake. The results suggest that noradrenaline released from the sympathetic nerve terminals by ischemic periods of between 10 and 40 min is not due to exocytosis, but to a carrier-mediated efflux using the same carrier as is normally responsible for transporting noradrenaline from the synaptic clefts back into the neuron.(ABSTRACT TRUNCATED AT 250 WORDS)
A
A
Schömig
A M
AM
Dart
R
R
Dietz
W
W
Kübler
E
E
Mayer
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism*; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002118:Calcium; D009638:Norepinephrine