Angiotensin-(1-7) blocks the angiotensin II-stimulated superoxide production

POLIZIO, ARIEL H.; GIRONACCI, MARIELA M.; TOMARO, MARÍA L.; PEÑA, CLARA

PHARMACOLOGICAL RESEARCH

Elsevier

Lugar: Amsterdam; Año: 2007 vol. 56 p. 86 - 90

1043-6618

Angiotensin (Ang)-(1–7), a bioactive compound of the renin–angiotensin system, exerts effects leading to blood pressure reduction which counterbalance Ang II pressor actions. The present study was conducted to examine Ang-(1–7) and Ang II effects on superoxide anion production in rat aorta using the lucigenin chemiluminescence method. Ang II dose-dependently increased superoxide anion formation when compared to control levels; a maximal increase (2.5-fold) was observed with 1x10-10 M peptide concentration. The Ang II-stimulated superoxide formation was blocked by 1x10-10 M losartan, the specific AT1 receptor antagonist, but not by 1x10-10 M PD 123319, the AT2 receptor antagonist, suggesting that the increased superoxide levels caused by Ang II are mediated through AT1 receptors activation. The Ang II-stimulated superoxide production was not modified by 2x10-8 M allopurinol or 1x10-7 M indomethacin, but was completely abolished by NAD(P)H oxidase inhibitors: 1x10-8 M diphenylene iodonium, or 2x10-8 M apocynin, demonstrating that NAD(P)H oxidase participates in such response. In contrast to Ang II, Ang-(1–7) concentrations ranging 1x10-12 to 1x10-6 M did not modify superoxide anion levels, but prevented the Ang II-enhanced superoxide production. In conclusion, we demonstrated that Ang-(1–7) blocks the pro-oxidant effects of Ang II, thus reducing the superoxide anion production and delaying the hypertension development.