Receptor-independent intracellular radical scavenging activity of an angiotensin II receptor blocker

• DOI: 10.1097/hjh.0b013e328165d159
• Publication Date: 2007-07-09T08:05:22Z
• Authors: Jing Shao; Masaomi Nangaku; Reiko Inagi; Hideki Kato; Toshio Miyata; Taiji Matsusaka; Eisei Noiri; Toshiro Fujita
• Keywords: Telmisartan

Objectives Angiotensin II plays a crucial role in the induction of oxidative stress and pathogenesis cardiovascular renal diseases, beneficial mechanisms angiotensin receptor 1 blockers (ARBs) are multifactorial. We investigated receptor-independent protective an ARB using primary-cultured mesangial cells from knockout or wild-type mice highly lipophilic ARB, telmisartan. Methods results Intracellular reactive oxygen species were estimated fluorogenic probe, CM-H2DCFDA. Non-angiotensin II-induced production was generated by exposing to hydrogen peroxide alone after treatment with Flow cytometry analysis showed that induced increase oxidant dose-dependent manner cells, but not cells. In contrast, both Interestingly, telmisartan attenuated suggesting it acted via antioxidant effect. concentrations confirmed high-performance liquid chromatography analysis. Expression plasminogen activator inhibitor 1, which is stimulated stress, also as well receptor-dependent manner. Telmisartan did change expression levels antioxidative enzymes such catalase glutathione peroxidase. Furthermore, amelioration involve peroxisome proliferator-activated receptor-γ pathway. Conclusions inhibits intracellular at least part, manner, possibly owing its structure.