title: Arginase-endothelial nitric oxide synthase imbalance contributes to endothelial dysfunction during chronic intermittent hypoxia.
abstract: OBJECTIVE
  Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnoea, is associated with impaired vascular function despite unaltered response to nitric oxide donors. This study addressed whether arginase contributes to the endothelial dysfunction in CIH rats.
  
  
  METHODS
  Adult male Sprague-Dawley rats were exposed for 21 days to CIH (5% oxygen, 12 times/h, 8 h/day). The internal carotid arteries were isolated to study endothelial nitric oxide synthase (eNOS) and arginase-1 levels by western blot and immunohistochemistry, and their vasoactive responses using wire myography. Relaxation to sodium nitroprusside (SNP; nitric oxide donor) in the presence or absence of soluble guanylyl cyclase inhibitor, and acetylcholine with and without a NOS inhibitor [N(G)-nitro-L-arginine (L-NA)] and the arginase inhibitor BEC were determined.
  
  
  RESULTS
  Arteries from the CIH rats presented higher active contraction induced by KCl (3.5 ± 0.4 vs. 2.3 ± 0.2 N/m2), augmented media-to-lumen ratio (∼40%), decreased relaxation to acetylcholine (12.8 ± 1.5 vs. 30.5 ± 4.6%) and increased sensitivity to SNP (pD2 7.3 ± 0.1 vs. 6.7 ± 0.1). Arginase inhibition reversed the impaired acetylcholine-induced relaxation in CIH arteries (49.5 ± 7.4%), an effect completely blocked by L-NA. In the carotid arteries, arginase-1 protein level was increased, whereas eNOS levels decreased in the CIH arteries.
  
  
  CONCLUSIONS
  The current results suggest that endothelial dysfunction in CIH-induced hypertension may result from imbalanced arginase-1 to eNOS expression, vascular remodelling and increased contractile capacity, rather than decreased vascular response to nitric oxide.
authors: aDivision of Obstetrics and Gynaecology bDivision of Paediatrics, Faculty of Medicine, School of Medicine cLaboratory of Neurobiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile dLaboratory of Cardiorespiratory Control, Center of Biomedical Research, Universidad Autónoma de Chile, Santiago, Chile.
authors: Bernardo J
authors: BJ
authors: Krause
authors: Rodrigo
authors: R
authors: Del Rio
authors: Esteban A
authors: EA
authors: Moya
authors: Monica
authors: M
authors: Marquez-Gutierrez
authors: Paola
authors: P
authors: Casanello
authors: Rodrigo
authors: R
authors: Iturriaga
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001158:Arteries / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C574619:ARG1 protein, human; D001119:Arginase; D000109:Acetylcholine