Angiotensin-(1–7) inhibits the angiotensin II-enhanced norepinephrine release in coarcted hypertensive rats

Since it has been suggested that angiotensin (Ang) (1–7) functions as an antihypertensive peptide, we studied its effect on the Ang II-enhanced norepinephrine (NE) release evoked by K + in hypothalami isolated from aortic coarcted hypertensive (CH) rats. The endogenous NE stores were labeled by incubation of the tissues with 3H-NE during 30 min, and after 90 min of washing, they were incubated in Krebs solution containing 25 mM KCl in the absence or presence of the peptides. Ang-(1–7) not only diminished the K +-evoked NE release from hypothalami of CH rats, but also blocked the Ang II-enhanced NE release induced by K +. Ang-(1–7) blocking action on the Ang II response was prevented by [ d-Ala 7]Ang-(1–7), an Ang-(1–7) specific antagonist, by PD 123319, an AT 2-receptor antagonist, and by Hoe 140, a B 2 receptor antagonist. Ang-(1–7) inhibitory effect on the Ang II facilitatory effect on K +-stimulated NE release disappeared in the presence of N ω-nitro- l-arginine methylester and was restored by l-arginine. Our present results suggest that Ang-(1–7) may contribute to blood pressure regulation by blocking Ang II actions on NE release at the central level. This inhibitory effect is a nitric oxide-mediated mechanism involving AT 2 receptors and/or Ang-(1–7) specific receptors and local bradykinin generation.