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

• MeSH
• 1-fosfatidylinositol-3-kinasa metabolismus   MeSH
• aktivace enzymů MeSH
• antihypertenziva farmakologie   MeSH
• benzimidazoly farmakologie   MeSH
• benzoáty farmakologie   MeSH
• blokátory receptoru 1 pro angiotenzin II farmakologie   MeSH
• časové faktory MeSH
• endoteliální buňky účinky léků   enzymologie   MeSH
• hypertenze farmakoterapie   enzymologie   genetika   patofyziologie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• modely nemocí na zvířatech MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• proteinkinasy aktivované AMP metabolismus   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• superoxiddismutasa metabolismus   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• B-lymfocyty cytologie   fyziologie   imunologie   MeSH
• buňky NK fyziologie   imunologie   MeSH
• CD4-pozitivní T-lymfocyty cytologie   fyziologie   imunologie   MeSH
• CD8-pozitivní T-lymfocyty fyziologie   imunologie   MeSH
• Escherichia coli genetika   imunologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• myši inbrední ICR fyziologie   imunologie   krev   MeSH
• receptory TNF fyziologie   imunologie   krev   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH