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-Ala7]Ang-(1-7), an Ang-(1-7) specific antagonist, by PD 123319, an AT2-receptor antagonist, and by Hoe 140, a B2 receptor antagonist. Ang-(1-7) inhibitory effect on the Ang II facilitatory effect on K+-stimulated NE release disappeared in the presence of Nomega-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 AT2 receptors and/or Ang-(1-7) specific receptors and local bradykinin generation.
Gironacci
Mariela Mercedes
MM
Departamento de Química Biológica e Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113, Buenos Aires, Argentina.
Yujnovsky
Irene
I
Gorzalczany
Susana
S
Taira
Carlos
C
Peña
Clara
C
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001017:Aortic Coarctation / Q000150:complications; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D000804:Angiotensin II; C073402:PD 123319; D009569:Nitric Oxide; C065679:icatibant; D000803:Angiotensin I; C118790:angiotensin I (1-7); D011188:Potassium; D001920:Bradykinin; D009638:Norepinephrine