title: Rho kinase inhibition by fasudil exerts antioxidant effects in hypercholesterolemic rats.
abstract: 1. The inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions, but the role of ROCK in oxidative stress in hypercholesterolemic rats has not been explored. The aim of the current study was to investigate the antioxidant effects and the potential related mechanisms of fasudil, a selective ROCK inhibitor, in high-cholesterol diet (HCD)-induced hypercholesterolemic rats. 2. Hypercholesterolemia was induced in rats by feeding with a HCD for 4 weeks. Starting from day 15, physiological saline (1 mL/100 g) or ROCK inhibitor, fasudil (10 or 30 mg/kg), was injected intraperitoneally for another 14 days. 3. The results showed that fasudil significantly suppressed ROCK activity, potently elevated the activities of antioxidant enzymes and the expression of endothelial nitric oxide synthase, as well as the concentration of nitric oxide in the serum and cardiac tissue. In addition, fasudil notably suppressed the extent of lipid peroxidation and attenuated the histopathological changes in the heart and liver of hypercholesterolemic rats. 4. These antioxidant effects of fasudil suggest that ROCK activation is involved in oxidative stress in hypercholesterolemic rats.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Ma
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.forename: Ensheng
authors.initials: E
authors.lastname: Ji
authors.forename: Gang
authors.initials: G
authors.lastname: Cao
authors.forename: Guoming
authors.initials: G
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Chu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006321:Heart; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000975:Antioxidants; D002791:Cholesterol, Dietary; D047428:Protein Kinase Inhibitors; D009569:Nitric Oxide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases; C049347:fasudil