Nitric oxide-mediated regulation of transepithelial sodium and chloride transport in murine nasal epithelium

Transepithelial ion transport is regulated by a variety of cellular factors . In light of recent evidence that nitric oxide (NO) production is decrease d in cystic fibrosis airways, we examined the role of NO in regulating sodi um and chloride transport in murine nasal epithelium. Acute intervention wi th the inducible NO synthase (iNOS)-selective inhibitor S-methylisothiourea resulted in an increase of amiloride-sensitive sodium absorption observed as a hyperpolarization of nasal transepithelial potential difference. Inhib ition of iNOS expression with dexamethasone also hyperpolarized transepithe lial potential difference, but only a portion of this increase proved to be amiloride sensitive. Chloride secretion was significantly inhibited in C57 BL/6J mice by the addition of both S-methylisothiourea and dexamethasone. M ice lacking iNOS expression [NOS2(-/-)] also had a decreased chloride-secre tory response compared with control mice. These data suggest that constitut ive NO production likely plays some role in the downregulation of sodium ab sorption and leads to an increase in transepithelial chloride secretion.