Prejunctional angiotensin receptors involved in the facilitation of noradrenaline release in mouse tissues

1 The effect of angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1-7) on the electrically induced release of noradrenaline was studied in preparations of mouse atria, spleen, hippocampus, occipito-parietal cortex and hypothalamus preincubated with [(3)H]-noradrenaline, The prejunctional angiotensin receptor type was investigated using the non-selective receptor antagonist saralasin (AT(1)/AT(2)) and the AT(1) and AT(2) selective receptor antagonists losartan and PD 123319, respectively. 2 In atrial and splenic preparations, angiotensin II (0.01 nM-0.1 mu M) and angiotensin III (0.01 and 0.1 nM-1 mu M) increased the stimulation-induced overflow of tritium in a concentration-dependent manner. Angiotensin IV, only at high concentrations (1 and 10 mu M), enhanced tritium overflow in the atria, while angiotensin-(1-7) (0.1 nM-10 mu M) was without effect in both preparations. 3 In preparations of hippocampus, occipito-parietal cortex and hypothalamus, none of the angiotensin peptides altered the evoked overflow of tritium. 4 In atrial and splenic preparations, saralasin (0.1 mu M) and losartan (0.1 and 1 mu M), but not PD 123319 (0.1 mu M), shifted the concentration-response curves of angiotensin II and angiotensin III to the right. 5 In conclusion, in mouse atria and spleen, angiotensin II and angiotensin III facilitate the action potential induced release of noradrenaline via a prejunctional ATI receptor. Only high concentrations of angiotensin TV are effective in the atria and angiotensin-(1-7) is without effect in both preparations. In mouse brain areas, angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1-7) do not modulate the release of noradrenaline.