AT-1 Receptor and Phospholipase C Are Involved in Angiotensin III Modulation of Hypothalamic Noradrenergic Transmission

MURIEL RODRÍGUEZ CAMPOS; CARINA KADARIÁN; VALERIA RODANO; LILIANA G. BIANCIOTTI; BELISARIO E. FERNANDEZ; MARCELO S. VATTA

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

Lugar: New York; Año: 2000 vol. 20 p. 747 - 762

0272-4340

Abstract SUMMARY 1. We previously reported that angiotensin III modulates noradrenergic neurotransmission in the hypothalamus of the rat. In the present work we studied the effects of angiotensin III on norepinephrine release and tyrosine hydroxylase activity. We also investigated the receptors and intracellular pathways involved in angiotensin III modulation of noradrenergic transmission. 2. In rat hypothalamic tissue labeled with [3H]norepinephrine 1, 10, and 100 nM and 1 μM losartan (AT1 receptor antagonist) had no effect on basal neuronal norepinephrine release, whereas 10 and 100 nM and 1 μM losartan partially diminished norepinephrine secretion evoked by 25 mM KCl. The AT2 receptor antagonist PD 123319 showed no effect either on basal or evoked norepinephrine release. The increase in both basal and evoked norepinephrine output induced by 1 μM angiotensin III was blocked by 1 μM losartan, but not by 1 μM PD 123319. 3. The phospholipase C inhibitor 5 μM neomicin inhibited the increase in basal and evoked norepinephrine release produced by 1 μM angiotensin III. 4. Tyrosine hydroxylase activity was increased by 1 μM angiotensin III and this effect was blocked by 1 μM LST and 5 μM neomicin, but not by PD 123319. On the other hand, 1 μM angiotensin III enhanced phosphatidyl inositol hydrolysis that was blocked by 1 μM losartan and 5 μM neomicin. PD 123319 (1 μM) did not affect ANG III-induced phosphatidyl inositol hydrolysis enhancement. 5. Our results confirm that angiotensin III acts as a modulator of noradrenergic transmission at the hypothalamic level through the AT1-phospholipase C pathway. This enhancement of hypothalamic noradrenergic activity suggests that angiotensin III may act as a central modulator of several biological processes regulated at this level by catecholamines, such as cardiovascular, endocrine, and autonomic functions as well as water and saline homeostasis.