title: Nitric oxide interferes with hypoxia signaling during colonic inflammation.
abstract: Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling.
  
  
  
  We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation.
  
  
  
  Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin) was assessed using Western blotting.
  
  
  
  The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression.
  
  
  
  Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.
authors.affiliation: Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil.
authors.forename: Cintia Rabelo e Paiva
authors.initials: CR
authors.lastname: Caria
authors.affiliation: Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil.
authors.forename: Camila Henrique
authors.initials: CH
authors.lastname: Moscato
authors.affiliation: Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil.
authors.forename: Renata Bortolin Guerra
authors.initials: RB
authors.lastname: Tomé
authors.affiliation: Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil.
authors.forename: José
authors.initials: J
authors.lastname: Pedrazzoli
authors.affiliation: Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil.
authors.forename: Marcelo Lima
authors.initials: ML
authors.lastname: Ribeiro
authors.affiliation: Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambero
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D017208:Rats, Wistar
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide