Acceleration of catecholamine biosynthesis in sympathetically innervated tissues by angiotensin-II-amide.

1. The effect of angiotensin-II-amide on the biosynthesis of catecholamines (CA) has been studied in a number of isolated tissues in vitro.2. Angiotensin increased the synthesis of CA from (14)C-tyrosine in guinea-pig atria and portal vein, in rat vasa deferentia and the rabbit portal vein.3. Angiotensin had no effect on synthesis of CA from (14)C-labelled DL-DOPA.4. The conditions required to demonstrate an increased synthesis were critical with respect to incubation time and angiotensin concentration. Effects were most readily apparent after incubation for 1 h with concentrations of angiotensin ranging from 10(-9) to 10(-7)M. Higher concentrations caused a significant reduction in synthesis.5. An increased release of newly synthesized CA into the incubation medium was sometimes seen in the presence of angiotensin. However, there was no correlation between increased synthesis and release of CA.6. Angiotensin was rapidly destroyed when incubated with guinea-pig or rat tissues in Krebs solution. The increase in CA synthesis was only apparent at a time when the incubation medium could have contained only a fraction of the original angiotensin activity.7. It is concluded that the effect of angiotensin is not due to increased release of noradrenaline (NA) or to inhibition of NA uptake into nerves. It is possible that angiotensin may influence the activity of tyrosine hydroxylase or its cofactors by an as yet unknown mechanism.