Effect of nitric oxide on epithelial ion transports in noncystic fibrosis and cystic fibrosis human proximal and distal airways

The airways of patients with cystic fibrosis (CF) exhibit decreased nitric oxide (NO) concentrations, which might affect airway function. The aim of this study was to determine the effects of NO on ion transport in human airway epithelia. Primary cultures of non-CF and CF bronchial and bronchiolar e...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2012-10, Vol.303 (7), p.L617-L625
Main Authors: Blouquit-Laye, Sabine, Dannhoffer, Luc, Braun, Camille, Dinh-Xuan, Anh-Tuan, Sage, Edouard, Chinet, Thierry
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
Adult
Aged
Amiloride - pharmacology
Bronchi - drug effects
Cells
Chloride Channels - drug effects
Colforsin - pharmacology
Cyclic GMP - analogs & derivatives
Cyclic GMP - analysis
Cyclic GMP - pharmacology
Cyclic N-Oxides - pharmacology
Cystic fibrosis
Cystic Fibrosis - drug therapy
Enzymes
Epithelial Sodium Channel Blockers - pharmacology
Epithelial Sodium Channels - drug effects
Free Radical Scavengers - pharmacology
Guanylate Cyclase - antagonists & inhibitors
Humans
Imidazoles - pharmacology
Lungs
Middle Aged
Nitric oxide
Nitric Oxide - pharmacology
Nitric Oxide Donors - pharmacology
Nitroprusside - pharmacology
Oxadiazoles - pharmacology
Purinones - pharmacology
Quinoxalines - pharmacology
Young Adult
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Summary:The airways of patients with cystic fibrosis (CF) exhibit decreased nitric oxide (NO) concentrations, which might affect airway function. The aim of this study was to determine the effects of NO on ion transport in human airway epithelia. Primary cultures of non-CF and CF bronchial and bronchiolar epithelial cells were exposed to the NO donor sodium nitroprusside (SNP), and bioelectric variables were measured in Ussing chambers. Amiloride was added to inhibit the Na(+) channel ENaC, and forskolin and ATP were added successively to stimulate cAMP- and Ca(2+)-dependent Cl(-) secretions, respectively. The involvement of cGMP was assessed by measuring the intracellular cGMP concentration in bronchial cells exposed to SNP and the ion transports in cultures exposed to 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, an inhibitor of the soluble guanylate cyclase (ODQ), or to 8Z, a cocktail of 8-bromo-cGMP and zaprinast (phosphodiesterase 5 inhibitor). SNP decreased the baseline short-circuit current (I(sc)) and the changes in I(sc) induced by amiloride, forskolin, and ATP in non-CF bronchial and bronchiolar cultures. The mechanism of this inhibition was studied in bronchial cells. SNP increased the intracellular cGMP concentration ([cGMP](i)). The inhibitory effect of SNP was abolished by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, an NO scavenger (PTIO) and ODQ and was partly mimicked by increasing [cGMP](i). In CF cultures, SNP did not significantly modify ion transport; in CF bronchial cells, 8Z had no effect; however, SNP increased the [cGMP](i). In conclusion, exogenous NO may reduce transepithelial Na(+) absorption and Cl(-) secretion in human non-CF airway epithelia through a cGMP-dependent pathway. In CF airways, the NO/cGMP pathway appears to exert no effect on transepithelial ion transport.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00368.2011