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

Abstract

. When animals were exposed to a temperature of 4° 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. . Increased sympathetic nervous activity associated with cold resulted in a four‐fold increase in rate of synthesis of noradrenaline. . Reduction in endogenous and labelled catecholamine levels associated with cold was exaggerated by pretreatment with cocaine, imipramine or phenoxy‐benzamine—drugs known to inhibit the uptake of noradrenaline into the nerve terminal. . 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. . 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.

Potassium Deficiency and Cardiac Catecholamine Metabolism in the Rat

“…Inhibition of monoamine oxidase also increases tissue norepinephrine and reduces turnover of catecholamines (23,41). This effect is similar to that seen with ganglionic blockade, but a proposed mechanism suggests that it is due to 614 KRAKOFF reduced intraneural catabolism of norepinephrine, which results in feedback inhibition of catecholamine synthesis (23,34).…”

Catecholamines in Blood and Myocardial Tissue in Experimental Subarachnoidal Hemorrhage

“…These values are lower than normal (table I). 2 One can easily induce this type of T peaks by injecting a small dose of nor adrenaline intravenously. Such T peaks are early electrocardiographic manifestations of noradrenaline action.…”

“…In an attempt to verify this hypothesis, some investigators have meas ured the urinary output of catecholamines in patients suffering from meningeal hemorrhage [14,19,[22][23][24], Others have tried to determine the amount of catecholamines in tissues (especially myocardium), in situations implying pronounced orthosympathic excitation [2,4,5,9,12,15,18,24]. In this study we report and discuss the results of blood and tissue determination of adrenaline and noradrenaline in dogs suffering from ESH.…”

Effect of reserpine on the activity of adrenal enzymes involved in the synthesis of adrenaline

“…Procedures which cause an increase in the activity of sympathetic nerves, such as direct nerve stimulation (Alousi & Weiner, 1966 ; Bhagat, 1967;Sedvall & Kopin, 1967a;Sedvall & Kopin, 1967b) or a reflex increase in sympathetic discharge (Bhagat & Friedman, 1969;Dairman, Gordon, Spector, Sjoerdsma & Udenfriend, 1968;Dairman & Udenfriend, 1970; Gordon, Spector, Sjoerdsma & Udenfriend, 1966) cause an almost immediate increase in the rate of synthesis of catecholamines due, perhaps, to increased activity of tyrosine hydroxylase (TH). Because the increase in enzymatic activity occurs without an increase in the amount of enzyme (Dairman et al, 1968;Sedvall & Kopin, 1967b), this phenomenon may be a consequence of the release of tyrosine hydroxylase from end-product inhibition.…”