Angiotensin-(1-7) blocks the angiotensin II-stimulated superoxide production.
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 1 x 10(-10)M peptide concentration. The Ang II-stimulated superoxide formation was blocked by 1 x 10(-10)M losartan, the specific AT(1) receptor antagonist, but not by 1 x 10(-10)M PD 123319, the AT(2) receptor antagonist, suggesting that the increased superoxide levels caused by Ang II are mediated through AT(1) receptors activation. The Ang II-stimulated superoxide production was not modified by 2 x 10(-8)M allopurinol or 1 x 10(-7)M indomethacin, but was completely abolished by NAD(P)H oxidase inhibitors: 1 x 10(-8)M diphenylene iodonium, or 2 x 10(-8)M apocynin, demonstrating that NAD(P)H oxidase participates in such response. In contrast to Ang II, Ang-(1-7) concentrations ranging 1 x 10(-12) to 1 x 10(-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.
Polizio
Ariel Héctor
AH
Departamento de Química Biológica, Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
Gironacci
Mariela Mercedes
MM
Tomaro
Maria Luján
ML
Peña
Clara
C
D000098:Acetophenones / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
C092006:7-Ala-angiotensin (1-7); D000098:Acetophenones; D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009861:Onium Compounds; D010446:Peptide Fragments; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; D013481:Superoxides; D000804:Angiotensin II; C073402:PD 123319; D000493:Allopurinol; C007517:diphenyleneiodonium; D000803:Angiotensin I; C056165:acetovanillone; D009247:NADH, NADPH Oxidoreductases; C118790:angiotensin I (1-7); D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin