Administration of telmisartan reduced systolic blood pressure and oxidative stress

14 We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on 15 the regulation of systolic blood pressure (SBP) and oxidative stress through 16 endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHR). SHRs 17 randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every 18 day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat 19 was measured before and weekly thereafter. After a total of 8-week treatment, rats 20 were killed for experimental measurements. Parameters that subject to measurements 21 in isolated aorta endothelial cells include: NO concentration, protein expression levels 22 of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and 23 eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also 24 applied to test the inhibition of NO concentration. We found that SBPs were 25 significantly lower in telmisartan therapy group than in placebo treated hypertensive 26 rats and WKYs (p < 0.05). The NO concentration was significantly higher in 27 telmisartan-treated group with increased activity of the PI3K/Akt pathway and 28 activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation 29 of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment 30 reduced less NO concentration in SHR rats than the telmisartan co-treated groups. 31 Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by 32 reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. 33 Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK 34 phosphorylation and eNOS expression, which attenuated the blood pressure and 35 oxidative stress in SHRs. 36