Effects of glycerol acetonide on adrenergic neurotransmission in isolated rabbit heart

In the present investigation, the solvent glycerol acetonide (GA, CAS 100-79-8) was added (110 mg/min) to the Tyrode buffer perfusing an isolated rabbit heart preloaded with 14C-noradrenaline (NA). GA inhibits the neuronal uptake of NA but stimulates its spontaneous release. The latter effect was not ascribed to the stimulation of NA biosynthesis or to an inhibition of its catabolism. Moreover GA inhibits the evoked-release of the transmitter by tyramine and dimethyl phenyl piperazinium (DMPP). By stimulating the spontaneous release of NA, GA may induce both a depletion of myocardial stores and an important increase of the transmitter, inhibiting thereby the evoked-release by a negative feed-back mechanism on presynaptic alpha 2 adrenoceptors. Hence, the impact of GA on some steps of the cardiac adrenergic transmission may provide an adequate explanation for its observed hypotensive effect.