Factors involved in maintenance of cardiac catecholamine content: relative importance of synthesis and re-uptake.

1. When animals were exposed to a temperature of 4 degrees C for 6 hr, endogenous catecholamines remained unaltered or reduced slightly depending upon the strain of rats used. In contrast, labelled noradrenaline declined rapidly, but the decline was inhibited when animals were pretreated with monoamine oxidase inhibitors.2. Increased sympathetic nervous activity associated with cold resulted in a four-fold increase in rate of synthesis of noradrenaline.3. Reduction in endogenous and labelled catecholamine levels associated with cold was exaggerated by pretreatment with cocaine, imipramine or phenoxybenzamine-drugs known to inhibit the uptake of noradrenaline into the nerve terminal.4. Cocaine and imipramine in higher doses inhibited the release of both endogenous and labelled noradrenaline, suggesting a dual action: in small doses they increased the depletion of catecholamines by blocking the reincorporation, while in higher doses they inhibited the release of noradrenaline.5. It is concluded that, under normal conditions, the re-uptake mechanism may not play a significant role in the maintenance of normal cardiac catecholamine levels and that such levels are maintained by synthesis alone. However, when the heart is subjected to high impulse nerve activity, synthesis is not sufficiently accelerated to compensate for impulse-induced massive release and may require the support of an additional mechanism, such as the partial reincorporation of released transmitter. In fact, the re-uptake mechanism is enhanced during high impulse activity.