Noradrenaline Release in the Human Pulmonary Artery is Modulated by Presynaptic α2Adrenoceptors

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Abstract
Summary: The mechanisms responsible for the local in-activation 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.