title: L-Arginine inhibiting pulmonary vascular remodelling is associated with promotion of apoptosis in pulmonary arterioles smooth muscle cells in broilers.
abstract: OBJECTIVE
  Pulmonary vascular remodelling is one of the important pathological bases of broiler pulmonary hypertension syndrome (PHS). Nitric oxide (NO) has been found to inhibit proliferation and to induce apoptosis in pulmonary artery smooth muscle cells (SMC) in mammals with pulmonary hypertension. The present study was conducted to evaluate the effects of NO precursor l-arginine on pulmonary vascular remodelling in broilers with pulmonary hypertension induced by cold exposure and to examine whether NO-induced apoptosis in pulmonary arteriole SMC is involved in the regulatory mechanisms.
  
  
  METHODS
  Two hundred and forty mixed-sex commercial broilers were equally assigned to three groups and reared in normal brooding temperatures before day 14. Starting on day 14 continuing until the end of the experiment, the control group was brooded in normal temperatures whereas the other two groups were subjected to low ambient temperatures with or without l-arginine added to the basal diets. Cumulative PHS mortality and body weight were recorded in each group. Right/total ventricle ratio (RV/TV), plasma NO concentration and pulmonary vascular morphological changes were analyzed. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay was used to detect apoptosis in pulmonary arteriole SMC.
  
  
  RESULTS
  l-Arginine, in group A, had no effect on body weights under cold temperature condition. Birds kept in group B had increased PHS mortality, RV/TV ratio, vessel wall area/vessel total area ratios (WA/TA) and mean media thickness in pulmonary arterioles (mMTPA) (P<0.05). Percentages of apoptotic SMC in pulmonary arterioles in group B were not altered by cold exposure (P>0.05). Supplemental dietary l-arginine in group A elevated plasma NO level (P<0.05), reduced PHS mortality (P<0.05), attenuated pulmonary vascular remodelling and increased the percentages of apoptotic SMC (P<0.05) when compared with the group B.
  
  
  CONCLUSIONS
  Supplemental l-arginine partially inhibited pulmonary vascular remodelling that occurred secondary to increased pulmonary pressure; NO-induced apoptosis in arteriole SMC might contribute to its regulatory effect on pulmonary vascular structural changes.
authors.affiliation: Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Tan
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: Pan
authors.forename: Jin-Chun
authors.initials: JC
authors.lastname: Li
authors.forename: Yan-Juan
authors.initials: YJ
authors.lastname: Liu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Sun
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000494:pharmacology*; D001160:Arterioles / Q000166:cytology; D001835:Body Weight / Q000187:drug effects; D002645:Chickens; D003080:Cold Temperature; D005260:Female; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000662:veterinary; D008168:Lung / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D009389:Neovascularization, Pathologic / Q000503:physiopathology* / Q000662:veterinary; D011201:Poultry Diseases / Q000503:physiopathology; D011651:Pulmonary Artery / Q000166:cytology*
chemical_list: D001120:Arginine