title: Chronic hydrogen-rich saline treatment reduces oxidative stress and attenuates left ventricular hypertrophy in spontaneous hypertensive rats.
abstract: In hypertensive animals and patients, oxidative stress represents the primary risk factor for progression of left ventricular hypertrophy. Recently, it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals and peroxynitrite anion to exert therapeutic antioxidant activity. In the current study, we explored the effect of chronic treatment with hydrogen-rich saline (HRS) on left ventricular hypertrophy in spontaneously hypertensive rats (SHR). The 8-week-old male SHR and age-matched Wistar-Kyoto rats (WKY) were randomized into HRS-treated (6 ml/kg/day for 3 months, i.p.) and vehicle-treated groups. HRS treatment had no significant effect on blood pressure, but it effectively attenuated left ventricular hypertrophy in SHR. HRS treatment abated oxidative stress, restored the activity of antioxidant enzymes including GPx, GST, catalase, and SOD, suppressed NADPH oxidase activity and downregulated Nox2 and Nox4 expression in left ventricles of SHR. HRS treatment suppressed pro-inflammatory cytokines including IL-1β, IL-6, TNF-α, and MCP-1, and inhibited NF-κB activation through preventing IκBα degradation in left ventricles of SHR. HRS treatment preserved mitochondrial function through restoring electron transport chain enzyme activity, repressing ROS formation, and enhancing ATP production in left ventricles of SHR. Moreover, HRS treatment suppressed ACE expression and locally reduced angiotensin II generation in left ventricles of SHR. In conclusion, HRS treatment attenuates left ventricular hypertrophy through abating oxidative stress, suppressing inflammatory process, preserving mitochondrial function, in which suppression of HRS on angiotensin II in left ventricles locally might be involved.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. yuys1982@hotmail.com
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Yu
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002374:Catalase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D006859:Hydrogen / Q000008:administration & dosage*; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008929:Mitochondria, Heart / Q000201:enzymology / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D012965:Sodium Chloride / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D045222:Electron Transport Chain Complex Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D030421:Peroxynitrous Acid; D012965:Sodium Chloride; D008315:Malondialdehyde; D006859:Hydrogen; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D005982:Glutathione Transferase