Angiotensin-(1-7) Reduces Norepinephrine Release Through a Nitric Oxide Mechanism in Rat Hypothalamus

GIRONACCI M; VATTA MS; RODRIGUEZ FERMEPIN M; FERNADEZ BE; PEÑA C

HYPERTENSION

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2000 vol. 35 p. 1248 - 1252

0194-911X

Angiotensin (Ang)-(1-7) elicits a facilitatory presynaptic effect on peripheral noradrenergic neurotransmission,and because biological responses to the heptapeptide on occasion are tissue specific, the present investigation wasundertaken to study its action on noradrenergic neurotransmission at the central level. In rat hypothalamus labeled with[3H]-norepinephrine, 100 to 600 nmol/L Ang-(1-7) diminished norepinephrine released by 25 mmol/L KCl. This effectwas blocked by the selective angiotensin type 2 receptor antagonist PD 123319 (1 mmol/L) and by the specific Ang-(1-7)receptor antagonist [D-Ala7]Ang-(1-7) (1 mmol/L) but not by losartan (10 nmol/L to 1 mmol/L), a selective angiotensintype 1 receptor antagonist. The inhibitory effect on noradrenergic neurotransmission caused by Ang-(1-7) was preventedby 10 mmol/L Nv-nitro-L-arginine methylester, an inhibitor of nitric oxide synthase activity, and was restored by100 mmol/L L-arginine, precursor of nitric oxide synthesis. Methylene blue (10 mmol/L), an inhibitor of guanylatecyclase considered as the target of nitric oxide action, as well as Hoe 140 (10 mmol/L), a bradykinin B2-receptorantagonist, prevented the inhibitory effect of the heptapeptide on neuronal norepinephrine release, whereas nomodification was observed in the presence of 0.1 to 10 mmol/L indomethacin, a cyclooxygenase inhibitor. Our resultsindicate that Ang-(1-7) has a tissue-specific neuromodulatory effect on noradrenergic neurotransmission, beinginhibitory at the central nervous system by a nitric oxide? dependent mechanism that involves angiotensin type 2receptors and local bradykinin production