RESUMEN
BACKGROUND AND PURPOSE: The aim of these experiments was to evaluate the significance of the chemical reaction between hydrogen sulphide (H2S) and nitric oxide (NO) for the control of vascular tone. EXPERIMENTAL APPROACH: The effect of sodium hydrosulphide (NaHS; H2S donor) and a range of NO donors, such as sodium nitroprusside (SNP), either alone or together, was determined using phenylephrine (PE)-precontracted rat aortic rings and on the blood pressure of anaesthetised rats. KEY RESULTS: Mixing NaHS with NO donors inhibited the vasorelaxant effect of NO both in vitro and in vivo. Low concentrations of NaHS or H2S gas in solution reversed the relaxant effect of acetylcholine (ACh, 400 nM) and histamine (100 microM) but not isoprenaline (400 nM). The effect of NaHS on the ACh response was antagonized by CuSO(4) (200 nM) but was unaffected by glibenclamide (10 microM). In contrast, high concentrations of NaHS (200-1600 microM) relaxed aortic rings directly, an effect reduced by glibenclamide but unaffected by CuSO4. Intravenous infusion of a low concentration of NaHS (10 micromol kg(-1) min(-1)) into the anaesthetized rat significantly increased mean arterial blood pressure. L-NAME (25 mg kg(-1), i.v.) pretreatment reduced this effect. CONCLUSIONS AND IMPLICATIONS: These results suggest that H2S and NO react together to form a molecule (possibly a nitrosothiol) which exhibits little or no vasorelaxant activity either in vitro or in vivo. We propose that a crucial, and hitherto unappreciated, role of H2S in the vascular system is the regulation of the availability of NO.
Asunto(s)
Aorta/metabolismo , Sulfuro de Hidrógeno/metabolismo , Óxido Nítrico/metabolismo , Animales , Aorta/fisiología , Presión Sanguínea , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND & AIMS: The factors that stimulate the growth of gastric mucosal cells during gastric mucosal healing are not completely understood. This study was designed to investigate the gene expression of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) in the healing of gastric mucosal lesions. METHODS: Northern blot analysis and reverse-transcription polymerase chain reaction were used to show HGF and KGF messenger RNA. RESULTS: Transcripts of HGF and KGF were not shown in rat gastric mucosal epithelium but were found in submucosal and muscular layers under normal conditions. When acute gastric mucosal lesions were induced by indomethacin treatment, expression of HGF messenger RNA was augmented in submucosal, muscular, or serosal layers, whereas the transcript of KGF was not influenced. When rat gastric mucosal epithelial cell line RGM1 and rat gastric mucosal primary culture cells were incubated with HGF or KGF, their proliferation was enhanced. CONCLUSIONS: The results showed increased gene expression of HGF together with constant production of KGF during gastric mucosal healing.
Asunto(s)
Factores de Crecimiento de Fibroblastos , Mucosa Gástrica/fisiología , Sustancias de Crecimiento/genética , Factor de Crecimiento de Hepatocito/genética , Queratinocitos/fisiología , Receptores de Factores de Crecimiento de Fibroblastos , Acetatos/farmacología , Ácido Acético , Animales , Secuencia de Bases , Línea Celular , Células Cultivadas , ADN/biosíntesis , Factor 10 de Crecimiento de Fibroblastos , Factor 7 de Crecimiento de Fibroblastos , Mucosa Gástrica/química , Expresión Génica , Hibridación in Situ , Indometacina/farmacología , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento/análisis , Úlcera Gástrica/metabolismoRESUMEN
Proliferating cells in the gastric mucosal epithelium were successfully enriched by counterflow elutriation in a medium-sized cell fraction. When inoculated on culture plates coated with E-C-L cell attachment matrix, these cells differentiated into mucus-producing cells after reaching confluence. Northern blot analysis did not detect any transcript of the proton pump, histidine decarboxylase, somatostatin, or pepsinogen I, indicating the absence of parietal, ECL, D, and chief cells in the confluent monolayer. These mucus-producing cell monolayers that respond to various growth factors may be a suitable model with which to investigate the function of gastric mucus cells in vitro.