Abstract 378: Angiotensin-(1-9) Decreases the Vascular Remodeling by Reducing Aorta Oxidative Stress of Hypertensive Rats by Angiotensin Ii Infusion

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Recently we found that Angiotensin (Ang)1-9 decreases the hypertension (HT) and exerts endothelial protective effects probably by antagonizing Ang II effects. We hypothesized here that Ang-(1-9) reduces HT and vascular remodeling induced by Ang II by inhibiting vascular oxidative stress.

Objective. To determine the effects of Ang-(1-9) in vascular oxidative stress of hypertensive rats by Ang II infusion.

Methods: Male rats were made hypertensives by long term continuous Ang II infusion. As controls (C) we used sham operated rats (n=26). Two weeks after Ang II infusion, the hypertensive rats were randomized to receive vehicle (H), n=22, Ang-(1-9) (600 ng/kg/min, n=24), Ang-(1-9) and Mas blocker receptor A779 (100 ng kg-1min-1, n=15) and Ang-(1-9) and AT2 receptor blocker PD123319 (36 ng kg-1min-1, n=14). Four weeks after Ang II infusion, systolic blood pressure (SBP, mmHg), aortic media thickness (AMT, μm), TGFβ1 and collagen I aortic (CA) levels (fold vs S), vascular reactivity Assays (VRA, % dilation at 10-9M AcCh), and aorta O2- production (O2-) and NADPH oxidase activity (NADPH) were determined.

Results. Hypertensive rats compared to sham rats had a significant increase (p<0.05) in SBP (C: 120 ± 1 vs H: 153 ± 4), AMT (C: 117 ± 3 vs H: 105 ± 1), TGFβ1 (C:1±0.1 vs H:1,7±0.3), CA (C:1 ± 0.3 vs H: 2.9 ± 0.6), O2- (C: 5200 ± 263 vs H: 14560 ± 402) and NADPH (C: 521 ± 34 vs H: 1212 ± 21) and sustained vasoconstriction. Compare to hypertensive rats , the chronic Ang-(1-9) administration significantly reduced SBP (127 ± 4), AMT (108 ±1), TGFb1 (0.6 ± 0.1), CA (0.9 ± 0.2), O2- (6230 ± 396) and NADPH (443 ± 18) and increased VRA (19.8 ± 2.3). These effects were reverted by PD123319 but not by A779.

Conclusion. The current study provides strong evidence for antihypertensive, vasodilatory and vascular protective effects of Ang-(1-9) by decreasing aorta oxidative stress of hypertensive rats. Fondecyt 1100874, Fondef D11I1122.

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