title: Prevention of diabetes-induced arginase activation and vascular dysfunction by Rho kinase (ROCK) knockout.
abstract: OBJECTIVE
  We determined the role of the Rho kinase (ROCK) isoforms in diabetes-induced vascular endothelial dysfunction and enhancement of arginase activity and expression.
  
  
  RESULTS
  Studies were performed in aortic tissues from haplo-insufficient (H-I) ROCK1 and ROCK2 mice and wild-type (WT) mice rendered diabetic with streptozotocin and in bovine aortic endothelial cells (BAECs) treated with high glucose (HG, 25 mM). Protein expression of both ROCK isoforms was substantially elevated in aortas of WT mice after 8 weeks of diabetes and in BAECs after 48 h in HG. Impairment of endothelium-dependent vasorelaxation of aortas was observed in diabetic WT mice. However, there was no impairment in aortas of diabetic ROCK1 H-I mice and less impairment in aortas of diabetic ROCK2 H-I mice, compared with non-diabetic mice. These vascular effects were associated with the prevention of diabetes-induced decrease in nitric oxide (NO) production and a rise in arginase activity/expression. Acute treatment with the arginase inhibitor, BEC, improved endothelium-dependent vasorelaxation of aortas of both diabetic WT and ROCK2, but not of ROCK1 mice.
  
  
  CONCLUSIONS
  Partial deletion of either ROCK isoform, but to a greater extent ROCK1, attenuates diabetes-induced vascular endothelial dysfunction by preventing increased arginase activity and expression and reduction in NO production in type 1 diabetes. Limiting ROCK and arginase activity improves vascular function in diabetes.
authors.affiliation: Department of Pharmacology and Toxicology,  Georgia Health Sciences University, Augusta, GA 30912-2300,  USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yao
authors.forename: Surabhi
authors.initials: S
authors.lastname: Chandra
authors.forename: Haroldo A
authors.initials: HA
authors.lastname: Toque
authors.forename: Anil
authors.initials: A
authors.lastname: Bhatta
authors.forename: Modesto
authors.initials: M
authors.lastname: Rojas
authors.forename: Ruth B
authors.initials: RB
authors.lastname: Caldwell
authors.forename: R William
authors.initials: RW
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology*; D001897:Boronic Acids / Q000494:pharmacology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D013311:Streptozocin / Q000009:adverse effects; D054460:rho-Associated Kinases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C425062:(2-boronoethyl)-cysteine; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D013311:Streptozocin; C515854:Rock1 protein, mouse; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases; D001119:Arginase; D020742:rhoA GTP-Binding Protein; D005947:Glucose