Release of endogenous noradrenaline from an isolated muscular artery

Abstract

1. The release of noradrenaline by field stimulation of vasoconstrictor nerves has been studied in isolated preparations of the main uterine artery of the guinea-pig.2. In preparations from virgin animals stimulation with trains of 3000 square pulses at 5 and 25 pulses/sec resulted in mean overflows of 0.56 ng/g.pulse and 1.53 ng/g.pulse respectively.3. Inhibition of monoamine oxidase and catechol-O-methyltransferase had no consistent effect on overflow at either stimulation frequency.4. Desmethylimipramine (10(-5)M) caused, on the average, a 2.4-fold increase in overflow following stimulation at 5 pulses/sec while phenoxybenzamine (10(-5)M) caused a 3.8-fold increase. Neither of these drugs caused a significant alteration of the overflow during stimulation at 25 pulses/sec.5. Treatment of the tissues with desmethylimipramine plus normetanephrine (4.5 x 10(-4)M) caused no more increase in overflow than treatment with desmethylimipramine alone.6. It is concluded that enzymatic metabolism of noradrenaline at the synapse is of little functional importance in this tissue, and that the most important mechanism of transmitter inactivation is by nervous re-uptake. Although phenoxybenzamine was more effective than desmethylimipramine in increasing transmitter overflow, no evidence was obtained to support the view that this effectiveness was due partly to blockade of ;Uptake 2'.7. There was sometimes very low overflow of noradrenaline from arteries taken from animals in the last week of pregnancy. In these instances overflow following stimulation at 5 pulses/sec was not increased by phenoxybenzamine treatment of the tissue.8. Methylene blue and fluorescence microscopic techniques indicated that the terminal adrenergic axons in each artery possess approximately 8.74 x 10(5) varicosities. The mean tissue content of noradrenaline was found to be 9.6 mug/g or 29 ng/artery. These results have been correlated with known morphological and electrophysiological data to derive a peak post-junctional concentration of noradrenaline during transmission of about 4 x 10(-4)M.9. The fraction of total noradrenaline content of the artery released per pulse (under the influence of phenoxybenzamine) had a mean value of 2.2 x 10(-4).