Evidence that angiotensin enhances transmitter release during sympathetic nerve stimulation

Abstract

The effects of angiotensin on the contractility of the transmurally stimulated rabbit portal vein and coeliac artery have been studied in conjunction with its effects on the release and uptake of (+)‐3H‐noradrenaline. Angiotensin contracted both vein and artery; these responses were enhanced by veratrine and reduced by tetradotoxin. At low (non‐contractile) concentrations of angiotensin, contractions elicited by electrical stimulation (0.5–4 Hz) had a quicker onset and reached a higher maximal tension than control responses. Higher concentrations of angiotensin increased the degree of potentiation. Contractions to noradrenaline were not enhanced by angiotensin. Pretreatment of the coeliac artery, portal vein and perfused rat heart with angiotensin did not reduce the subsequent uptake of labelled noradrenaline in the presence of angiotensin. Simultaneous treatment with angiotensin and 3H‐noradrenaline caused a small, apparent inhibition of uptake into the portal vein. When the portal vein was incubated with 3H‐noradrenaline there was a marked accumulation of label within the tissue; over 90% of the radioactivity retained in the tissue was identified as intact noradrenaline. When the vein, or artery, was superfused with amine‐free Krebs there was a steady basal release of label; the greater proportion of this label was identified as deaminated metabolites. Electrical stimulation evoked a frequency dependent release of 3H above basal levels. The greater proportion of this increased efflux was due to the release of intact 3H‐noradrenaline, with smaller increases in the amount of O‐methylated and deaminated metabolites. Angiotensin increased the efflux of labelled noradrenaline + normetanephrine, or of total 3H, during transmural stimulation (0.5–4 Hz) in both the vein and artery, but did not increase the efflux of deaminated products during electrical stimulation. The output of labelled noradrenaline + normetanephrine was usually doubled in the presence of angiotensin (200–500 ng/ml) during electrical stimulation of the portal vein. Cocaine (4 μg/ml) potentiated responses to noradrenaline and transmural stimulation, and doubled the output of 3H or labelled noradrenaline + normetanephrine during electrical stimulation. Cocaine did not alter the potentiating effects of angiotensin. Angiotensin elicited transitory increases in the basal efflux of 3H from both the portal vein and coeliac artery. However, this did not account for the marked increase in efflux seen during electrical stimulation. Vasopressin did not potentiate responses to transmural stimulation or significantly influence the efflux of 3H from the vein or artery. Noradrenaline and 5‐hydroxytryptamine, but not acetylcholine, markedly increased the efflux of 3H from the portal vein. This increase in efflux of label is believed to result from an exchange of exogenous noradrenaline and 5‐hydroxytryptamine with labelled tissue stores of noradrenaline. It is suggested that angiotensin is able to facilitate the release of the sympathetic transmitter and that this is the basis for its action in potentiating the responses to sympathetic stimulation. It is also suggested that the noradrenaline releasing action of angiotensin (by excitation of sympathetic nerve endings) has led to confusion in previous investigations of the effects of angiotensin on noradrenaline uptake. 1971 British Pharmacological Society