RESUMO
AIM: To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Helicobacter pylori (HPE). METHODS: The stomachs of isoflurane-anesthetized mice were exteriorized, and the mucosal surface exposed. Blood flow was measured with the laser-Doppler technique, and systemic arterial blood pressure monitored. C57BL/6 mice were exposed to water extract produced from H pylori strain 88-23. To investigate the role of a nerve- or iNOS-mediated pathway, we used intraluminal lidocaine and iNOS-/- mice. Blood flow response to the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine (ADMA) was also assessed. RESULTS: In wild-type mice, HPE decreased mucosal blood flow by approximately 30%. This reduction was abolished in iNOS-deficient mice, and by pre-treatment with lidocaine. Luminally applied ADMA resulted in reduction in blood flow similar to that observed in wild-type mice exposed to HPE. CONCLUSION: A H pylori water extract reduces gastric mucosal blood flow acutely through iNOS- and nerve-mediated pathways.
Assuntos
Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/microbiologia , Helicobacter pylori/patogenicidade , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/inervação , Helicobacter pylori/química , Lidocaína/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/deficiência , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/fisiologia , Transdução de Sinais/efeitos dos fármacos , ÁguaRESUMO
Mucus thickness is suggested to be related to mucosal protection. We therefore investigated the importance of the removable mucous layer and epithelial bicarbonate transport in preservation of the gastric juxtamucosal pH (pH(jm)) during luminal acid. Anesthetized rats were prepared for intravital microscopy of the gastric mucosa, and pH(jm) was measured with pH-sensitive microelectrodes. The mucus was either left intact (IM) or removed (MR) down to the firmly attached mucous layer, and HCl (pH 1) was applied luminally. Removal of the loosely adherent mucous layer did not influence the pH(jm) during luminal acid (pentagastrin: IM/MR 7.03 +/- 0.09/6.82 +/- 0.19; pentagastrin + indomethacin: IM/MR 6.89 +/- 0.20/6.95 +/- 0.27; ranitidine: IM/MR 2.38 +/- 0.64/2.97 +/- 0.62), unless prostaglandin synthesis and acid secretion were inhibited (ranitidine + indomethacin: IM/MR 2.03 +/- 0.37/1.66 +/- 0.18). Neutral pH(jm) is maintained during endogenous acid secretion and luminal pH 1, unless DIDS was applied luminally, which resulted in a substantially decreased pH(jm) (1.37 +/- 0.21). Neutral pH(jm) is maintained by a DIDS-sensitive bicarbonate transport over the surface epithelium. The loosely adherent mucous layer only contributes to maintaining pH(jm) during luminal pH 1 if acid secretion and prostaglandin synthesis are inhibited.