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Inducible nitric oxide synthase activity induced by sodium chloride solution prolongs luminal pH elevation in rat and mouse stomachs
Author(s) -
TATEMICHI MASAYUKI,
OGURA TSUTOMU,
SAKURAZAWA NOBUYUKI,
NAGATA HIROSHI,
SUGITA MINORU,
ESUMI HIROYASU
Publication year - 2003
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2003.03130.x
Subject(s) - nitric oxide synthase , tonicity , gastric mucosa , nitric oxide , sodium , medicine , microbiology and biotechnology , endocrinology , chemistry , stomach , biology , organic chemistry
Background: Sodium chloride (NaCl) is a strong promoter of gastric cancer. We hypothesized that inducible nitric oxide synthase (iNOS) induced by NaCl may be involved in its promoting effects. We investigated iNOS expression by hypertonic NaCl solutions and its pathophysiological roles in the gastric mucosa of rats and mice. Methods: iNOS mRNA and protein expressions were examined in the rat and mouse gastric mucosa after intragastric administration of NaCl solution by northern blot, reverse transcription‐polymerase chain reaction (RT‐PCR) and immunohistochemistry. The effect on luminal pH by iNOS activity was assessed using aminoguanidine, a potent iNOS inhibitor, and iNOS gene deficient (iNOS –/– ) mice. Results: iNOS expression was detected at concentrations higher than 1.7 M, mainly in the cells infiltrating the damaged mucosa of rats. Administration of a higher than 3.4 M NaCl solution elevated luminal pH of the rat stomach remarkably, enabling bacterial overgrowth and dramatically increasing iNOS expression ( n = 5 per concentration). Pretreatment with ampicillin (p.o), an antibiotic, attenuated the iNOS expression in duplicate experiments. Co‐treatment with aminoguanidine (s.q) accelerated recovery of elevated luminal pH at 8 h and 16 h or 24 h after administration of 3.4 M ( n = 8) and 5.2 M NaCl solution ( n = 5), respectively. iNOS expression and luminal pH elevation were also observed in mice stomachs after administration of 3.4 M NaCl solution. The elevated luminal pH of iNOS –/– mice stomachs after the administration of NaCl solution was significantly lower at 6 h ( n = 7) and at 9 h ( n = 11), compared to that of wild type mice ( n = 9 and 10, respectively). Conclusions: Hypertonic NaCl solutions induced iNOS expression in the gastric mucosa. iNOS activity prolonged the elevation of the luminal pH, potentially leading to bacterial overgrowth, which in turn enhanced iNOS expression. This vicious cycle might be related to the promoting effect of NaCl.