AT2 Receptors are Coupled to the Inhibitory Effect of Angiotensin-(1-7) on Central Noradrenergic Neurotranmission

pp 577-582

Abstract

Angiotensin [(Ang)-(1-7)] elicits a facilitatory presynaptic effect on peripheral noradrenergic neurotransmission. Since biological responses to the above mentioned heptapeptide are tissue specific, present investigation was undertaken to study Ang-(1-7) actions on noradrenergic neurotransmission at central nervous system level. In rat hypothalamus labeled with [3H]-noradrenaline (NA),100 to 600 nM Ang-(1-7) diminished NA re-leased by 25 mM KCI. This effect was blocked by the selective angiotensin type 2 receptor antagonist PD 123319 (0.1-1.μmol/L) but not by losartan(10 nmol/L to 1 μmol/L), a selective angiotensin type1 receptor antagonist. On the other hand, hypothalami incubated with[³H]NA in the presence of 0.1-10 μM Ang-(1-7)showed no modification in the [³H]NA content with respect to the con-trol group, suggesting that the heptapeptide did not modify [3H]NA neuronal uptake. To study the effect of the heptapeptide on NA catabolism, monoamine-oxidase (MAO) and catechol-O-me-thyl transferase (COMT) activities were measured.No significant changes with respect to the control group were observed in either hypothalamic MAO or COMT activities in the presence of Ang-(1-7)(0.1-1.0 μM).Our results indicate that Ang-(1-7) has a tissue-specific neuromodulatory effect on noradrenergic neurotransmission, being inhibitoryat the central nervous system, and mediated by angiotensin type 2receptors activation. Ang-(1-7) exerts such effect by inhibiting NA release, with-out affecting either the neurotransmitter neuronal uptake or catabolism.