Inhibition of neuronal noradrenaline uptake by angiotensin II in the rat mesentery

Abstract

In the isolated perfused rat mesentery, angiotensin II (3 × 10−9 M) in subpressor doses enhanced the vasoconstrictor responses to noradrenaline by 9.6 ± 1.4 mmHg. However, in mesenteries obtained from rats chemically sympathectomized with 6-hydroxydopamine, angiotensin II was without effect. Treatment of mesenteries with the noradrenaline neuronal uptake blockers desmethylimipramine (10−10 M), protriptyline (10−10 M), or cocaine (10−6 M) potentiated responses to noradrenaline by 3.8 ± 0.84, 3.7 ± 0.67, and 5.5 ± 0.26 mmHg, respectively. Angiotensin II alone or in combination with either desmethylimipramine, protriptyline, or cocaine potentiated the noradrenaline responses to a similar extent. On the other hand, corticosterone (1.5 × 10−6 M), an extraneuronal uptake blocker, enhanced noradrenaline responses by 4.3 ± 1.4 mmHg, and this enhancement was additive with the potentiation produced by cocaine and (or) angiotensin II. We conclude that angiotensin II in subpressor doses acts presynaptically to block selectively the neuronal uptake of noradrenaline without any appreciable effect on extraneuronal uptake.