title: The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model.
abstract: OBJECTIVE
  Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage, and a significant cause of morbidity and mortality. In this study, we have used a rabbit model of CDH to evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary artery.
  
  
  METHODS
  CDH was performed in New Zealand rabbit fetuses (n = 10 per group) and compared to controls. Measurements of body, total and left lung weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with phenylephrine (10 μM), after which cumulative concentration-response curves to glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770 (sGC activator) were obtained as well as the levels of NO (NO3/NO2).
  
  
  RESULTS
  LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the potency (pEC50) for GTN was markedly lower in CDH (8.25 ± 0.02 versus 9.27 ± 0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in CDH (11.7 ± 0.03 versus 10.5 ± 0.06; p < 0.01). The NO2/NO3 levels were 62 % higher in CDH (p < 0.05).
  
  
  CONCLUSIONS
  BAY 60-2770 exhibits a greater potency to relax the pulmonary artery in CDH, indicating a potential use for pulmonary hypertension in this disease.
authors: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, SP, Brazil.
authors: Julio Alejandro
authors: JA
authors: Rojas-Moscoso
authors: Edson
authors: E
authors: Antunes
authors: Rebeca Rodrigues
authors: RR
authors: Figueira
authors: Frances Lilian
authors: FL
authors: Gonçalves
authors: Ana Leda Bertoncioni
authors: AL
authors: Simões
authors: Lourenço
authors: L
authors: Sbragia
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D065630:Hernias, Diaphragmatic, Congenital; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects*; D011817:Rabbits
chemical_list: C528797:4-(((4-carboxybutyl) (2- (5-fluoro-2-((4'-(trifluoromethyl) biphenyl-4-yl)methoxy)phenyl)ethyl) amino)methyl)benzoic acid; D001565:Benzoates; D001713:Biphenyl Compounds; D006845:Hydrocarbons, Fluorinated