title: [Drug development for cardiorenal disease based on oxidative stress control].
abstract: Oxidative stress is a key factor involved in the pathogenesis and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). Reactive oxygen species (ROS), produced as a result of redox reactions in various cells, have been recognized as key chemical mediators causing cellular damage and organ dysfunction in CVD and CKD. Nifedipine, a well-known calcium channel blocker, is extremely sensitive to light which gets converted to its nitroso analog, nitrosonifedipine (NO-NIF) in the presence of ultraviolet and visible light. The so formed NO-NIF blocks calcium channel quite weakly compared to that of nifedipine. However, we elucidated for the first time that NO-NIF is converted to NO-NIF radical which acquires extremely strong antioxidant property via reaction with unsaturated fatty acid or endothelial cells. We have already reported that NO-NIF reduces the cytotoxicity of cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, in endothelial cells. Additionally, we demonstrated that NO-NIF restored acetylcholine-responsive vascular relaxation and suppressed intercellular adhesion molecule-1 expression in the aorta of N(ω)-nitro-L-arginine methyl ester-treated rats, a model of vascular endothelial dysfunction. Recently, we reported that NO-NIF ameliorates angiotensin II-induced vascular remodeling via antioxidative effects in vivo and in vitro. These observations point towards the plausible, unique role of NO-NIF as a novel antioxidant which improves vascular dysfunction for overcoming CVD and CKD and the same has been highlighted in this review.
authors.affiliation: Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School.
authors.forename: Masaki
authors.initials: M
authors.lastname: Imanishi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Takumi
authors.initials: T
authors.lastname: Sakurada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishizawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kihira
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D009603:Nitroso Compounds; D017382:Reactive Oxygen Species; C539379:nitrosonifedipine; D009569:Nitric Oxide; D009543:Nifedipine