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

RODRIGUEZ CAMPOS M; KADARIAN C; RODANO V; BIANCIOTTI LG; FERNADEZ BE; VATTA MS

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

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

0272-4340

1. We previously reported that angiotensin III modulates noradrenergic neurotransmissionin the hypothalamus of the rat. In the present work we studied the effects ofangiotensin III on norepinephrine release and tyrosine hydroxylase activity. We alsoinvestigated the receptors and intracellular pathways involved in angiotensin III modulationof noradrenergic transmission.2. In rat hypothalamic tissue labeled with [3H]norepinephrine 1, 10, and 100 nM and1 M losartan (AT1 receptor antagonist) had no effect on basal neuronal norepinephrinerelease, whereas 10 and 100 nM and 1 M losartan partially diminished norepinephrinesecretion evoked by 25 mM KCl. The AT2 receptor antagonist PD 123319 showed noeffect either on basal or evoked norepinephrine release. The increase in both basal andevoked norepinephrine output induced by 1 M angiotensin III was blocked by 1 Mlosartan, but not by 1 M PD 123319.3. The phospholipase C inhibitor 5 M neomicin inhibited the increase in basal andevoked norepinephrine release produced by 1 M angiotensin III.4. Tyrosine hydroxylase activity was increased by 1 M angiotensin III and this effectwas blocked by 1 M LST and 5 M neomicin, but not by PD 123319. On the other hand,1 M angiotensin III enhanced phosphatidyl inositol hydrolysis that was blocked by 1 Mlosartan and 5 Mneomicin. PD 123319 (1 M) did not affect ANGIII-induced phosphatidylinositol hydrolysis enhancement.5. Our results confirm that angiotensin III acts as a modulator of noradrenergictransmission at the hypothalamic level through the AT1-phospholipase C pathway. Thisenhancement of hypothalamic noradrenergic activity suggests that angiotensin III may actas a central modulator of several biological processes regulated at this level by catecholamines,such as cardiovascular, endocrine, and autonomic functions as well as water andsaline homeostasis.