Angiotensin III modulates noradrenaline uptake and release in the rat hypothalamus.

1. Effects of angiotensin III (A III) on 3H-noradrenaline (3H-NA) total, neuronal and non-neuronal uptake, 3H intracellular distribution and release were studied in vitro in the rat hypothalamus. 2. A III (1 microM) decreased total, neuronal and non-neuronal 3H-NA uptake when hypothalamic slices were incubated with 3H-NA for 30 min. A III effects on neuronal and non-neuronal 3H-NA uptake were determined in the presence of 100 microM hydrocortisone or 10 microM cocaine hydrochloride, respectively. The effect of A III on total 3H-NA uptake was blocked by 10 microM Ile7 angiotensin III (Ile7 A III), an antagonist at A III receptors. In contrast, 100 nM A III had no effect on 3H-NA uptake. 3. The study of the 3H-NA uptake time course showed that 1 microM AIII decreased NA uptake at 1, 3, 7, 15 and 30 min incubation. 4. In hypothalamic slices preloaded with 3H-NA for 30 min, 1 microM AIII increased the 3H content in the granular pool and decreased it in the cytosolic pool. 5. Spontaneous 3H release was also modified by 1 microM A III when hypothalami were preloaded with 3H-NA for 30 min. A III increased the spontaneous output of 3H. This effect was receptor-mediated since the effect of A III on 3H release was antagonized by Ile7 A III. 6. The present results suggest that the effects of A III on NA neurotransmission, may be involved in the regulation of central angiotensin effects such as blood pressure control, hydrosaline balance and dipsogenesis, through modulation of central sympathetic activity.