title: Chronic intermittent hypoxia-induced neuronal apoptosis in the hippocampus is attenuated by telmisartan through suppression of iNOS/NO and inhibition of lipid peroxidation and inflammatory responses.
abstract: Obstructive sleep apnea syndrome (OSAS) plays a critical role in the initiation and progression of Alzheimer׳s disease (AD), but little is known about the precise mechanism of OSAS-induced AD. Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play key roles in the development of AD. Several studies have confirmed that an angiotensin II type 1 receptor blocker, telmisartan, beneficially regulates NOS and NO. Here, we examined the neuroprotective effects of telmisartan against hippocampal apoptosis induced by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological change of OSAS. Adult male Sprague Dawley rats were subjected to 8h of intermittent hypoxia per day with or without telmisartan for eight weeks. Neuronal apoptosis in the hippocampal CA1 region, NOS activity, NO content, and the presence of inflammatory agents and radical oxygen species in the hippocampus were determined. The results showed that CIH activated inducible nitric oxide synthase (iNOS), increased NO content, and enhanced lipid peroxidation and inflammatory responses in the hippocampus. Treatment with telmisartan inhibited excessive iNOS and NO generation and reduced lipid peroxidation and inflammatory responses. In addition, telmisartan significantly ameliorated the hippocampal apoptosis induced by CIH. In conclusion, Pre-CIH telmisartan administration attenuated CIH-induced hippocampal apoptosis partly by regulating NOS activity, inhibiting excessive NO generation, and reducing lipid peroxidation and inflammatory responses.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Die
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, China. Electronic address: hgliu@tjh.tjmu.edu.cn.
authors.forename: Huiguo
authors.initials: H
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000473:pathology*; D000860:Hypoxia / Q000150:complications* / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology*; D015850:Interleukin-6 / Q000097:blood; D017493:Leukocyte Common Antigens / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D009569:Nitric Oxide; D002097:C-Reactive Protein; D052247:Nitric Oxide Synthase Type II; D017493:Leukocyte Common Antigens; D000077333:Telmisartan
keywords: Apoptosis; Chronic intermittent hypoxia; Hippocampus; Inflammation; NO synthases; Telmisartan