Nitric oxide interferes with hypoxia signaling during colonic inflammation.

Autor:	Caria CR; Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil., Moscato CH; Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil., Tomé RB; Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil., Pedrazzoli J Jr; Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil., Ribeiro ML; Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil., Gambero A; Unidade Integrada de Farmacologia e Gastroenterologia (Unifag), Faculdade de Medicina da Universidade São Francisco, São Paulo, SP, Brasil.
Jazyk:	angličtina
Zdroj:	Arquivos de gastroenterologia [Arq Gastroenterol] 2014 Oct-Dec; Vol. 51 (4), pp. 302-8.
DOI:	10.1590/S0004-28032014000400007
Abstrakt:	Context: 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. Objectives: We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods: 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. Results: 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. Conclusions: Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.
Databáze:	MEDLINE
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