title: Arginase promotes endothelial dysfunction and hypertension in obese rats.
abstract: OBJECTIVE
  This study investigated whether arginase contributes to endothelial dysfunction and hypertension in obese rats.
  
  
  METHODS
  Endothelial function and arginase expression were examined in skeletal muscle arterioles from lean and obese Zucker rats (ZRs). Arginase activity, arginine bioavailability, and blood pressure were measured in lean and obese animals.
  
  
  RESULTS
  Arginase activity and expression was increased while global arginine bioavailability decreased in obese ZRs. Acetylcholine or luminal flow caused dilation of isolated skeletal muscle arterioles, but this was reduced or absent in vessels from obese ZRs. Treatment of arterioles with a nitric oxide synthase inhibitor blocked dilation in lean arterioles and eliminated differences among lean and obese vessels. In contrast, arginase inhibitors or l-arginine enhanced vasodilation in obese ZRs and abolished differences between lean and obese animals, while d-arginine had no effect. Finally, mean arterial blood pressure was significantly increased in obese ZRs. However, administration of l-arginine or arginase inhibitors lowered blood pressure in obese but not lean animals, and this was associated with an improvement in systemic arginine bioavailability.
  
  
  CONCLUSIONS
  Arginase promotes endothelial dysfunction and hypertension in obesity by reducing arginine bioavailability. Therapeutic approaches targeting arginase represent a promising approach in treating obesity-related vascular disease.
authors.affiliation: Department of Molecular Sciences, Lincoln Memorial University, Harrogate, Tennessee, USA.
authors.forename: Fruzsina K
authors.initials: FK
authors.lastname: Johnson
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Peyton
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Azam
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Shebib
authors.forename: Robert A
authors.initials: RA
authors.lastname: Johnson
authors.forename: William
authors.initials: W
authors.lastname: Durante
mesh_terms: D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000235:genetics*; D001160:Arterioles / Q000201:enzymology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009765:Obesity / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D012313:RNA / Q000235:genetics*; D051381:Rats; D011924:Rats, Zucker; D060888:Real-Time Polymerase Chain Reaction; D014664:Vasodilation / Q000502:physiology*
chemical_list: D012313:RNA; D001119:Arginase