ANGIOTENSIN AND NOREPINEPHRINE EFFLUX

Rabbit aortae were equilibrated with labelled norepinephrine and the effects of various drugs on efflux of the catecholamine studied. Angiotensin amide (10 μg/ml) given at a rate of 0.18 ml/min increased norepinephrine efflux. Tyramine (100 μg/ml), cocaine (50 μg/ml), guanethidine (250 μg/ml), 0.25 and 0.4 M KCl, and acetylcholine (1 mg/ml) also increased norepinephrine efflux, whereas bethanidine (250 μg/ml) and bretylium (250 μg/ml) had no effect. Tyramine and guanethidine probably act by displacing norepinephrine from storage granules, whereas KCl, acetylcholine and probably angiotensin act by depolarizing neuronal membranes. Bretylium and bethanidine prevented the increased efflux seen after tyramine and angiotensin, probably by stabilizing the storage granule membrane, and preventing release of norepinephrine. Bretylium and bethanidine, however, increased efflux during KCl administration, possibly owing the inhibition of the catecholamine pump. It is concluded that angiotensin can release norepinephrine from tissue but the amount of angiotensin required is a thousand-fold in excess of that needed to inhibit norepinephrine uptake. © 1969.