Interactions of inhibitors of noradrenaline uptake and angiotensin on the sympathetic nerves of the isolated rabbit heart.

1. The interaction of angiotensin and several inhibitors of the uptake of noradrenaline across the neuronal membrane (cocaine, desipramine, protriptyline. and pronethalol) on the output of noradrenaline produced by sympathetic nerve stimulation has been studied in the isolated perfused rabbit heart.2. Most of these drugs increased noradrenaline outflow-angiotensin, for example, by 175%. Cocaine (10(-4)M) did not change the amine overflow, probably because this very high concentration inhibited not only the re-uptake but also the liberation of noradrenaline.3. Desipramine, protriptyline, and pronethalol, although infused in concentrations which enhanced the noradrenaline output, were not able to impair the angiotensin-induced increase of transmitter overflow. In the presence of cocaine (10(-4)M) the increase elicited by angiotensin was slightly reduced, though lower concentrations of cocaine, as previously described, do not interfere with the effect of angiotensin.4. In contrast to the interaction between uptake inhibitors and angiotensin, the augmented output of noradrenaline caused by an uptake inhibitor could not be increased further by infusion of a second uptake inhibitor.5. It is concluded that the increase of the outflow of noradrenaline during sympathetic nerve stimulation by small doses of angiotensin is not caused by an inhibition of re-uptake. On the contrary, the transmitter liberation seems to be facilitated. This is a novel principle of drug action on the sympathetic nerve terminals.