title: RhoA/rock signaling mediates peroxynitrite-induced functional impairment of Rat coronary vessels.
abstract: Diabetes-induced vascular dysfunction may arise from reduced nitric oxide (NO) availability, following interaction with superoxide to form peroxynitrite. Peroxynitrite can induce formation of 3-nitrotyrosine-modified proteins. RhoA/ROCK signaling is also involved in diabetes-induced vascular dysfunction. The study aimed to investigate possible links between Rho/ROCK signaling, hyperglycemia, and peroxynitrite in small coronary arteries.
  
  
  
  Rat small coronary arteries were exposed to normal (NG; 5.5 mM) or high (HG; 23 mM) D-glucose. Vascular ring constriction to 3 mM 4-aminopyridine and dilation to 1 μM forskolin were measured. Protein expression (immunohistochemistry and western blot), mRNA expression (real-time PCR), and protein activity (luminescence-based G-LISA and kinase activity spectroscopy assays) of RhoA, ROCK1, and ROCK2 were determined.
  
  
  
  Vascular ring constriction and dilation were smaller in the HG group than in the NG group (P < 0.05); inhibition of RhoA or ROCK partially reversed the effects of HG. Peroxynitrite impaired vascular ring constriction/dilation; this was partially reversed by inhibition of RhoA or ROCK. Protein and mRNA expressions of RhoA, ROCK1, and ROCK2 were higher under HG than NG (P < 0.05). This HG-induced upregulation was attenuated by inhibition of RhoA or ROCK (P < 0.05). HG increased RhoA, ROCK1, and ROCK2 activity (P < 0.05). Peroxynitrite also enhanced RhoA, ROCK1, and ROCK2 activity; these actions were partially inhibited by 100 μM urate (peroxynitrite scavenger). Exogenous peroxynitrite had no effect on the expression of the voltage-dependent K+channels 1.2 and 1.5.
  
  
  
  Peroxynitrite-induced coronary vascular dysfunction may be mediated, at least in part, through increased expressions and activities of RhoA, ROCK1, and ROCK2.
authors.affiliation: Department of Heart Center, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Heart Center, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Heart Center, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Heart Center, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Heart Center, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Shen
authors.affiliation: Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease, Beijing, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ma
authors.affiliation: Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease, Beijing, People's Republic of China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Heart Center, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China. lhw19656@sina.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D030421:Peroxynitrous Acid / Q000633:toxicity; D010766:Phosphorylation; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014661:Vasoconstriction / Q000502:physiology*; D054460:rho-Associated Kinases / Q000096:biosynthesis / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D030421:Peroxynitrous Acid; D012313:RNA; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: Coronary artery; Hyperglycemia; Peroxynitrite; RhoA/ROCK; Vasoconstriction; Vasodilation