Journal
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Volume 30, Issue 5, Pages 720-728Publisher
AMER THORACIC SOC
DOI: 10.1165/rcmb.2003-0325OC
Keywords
-
Funding
- NHLBI NIH HHS [1R01 HL071621, HL07918-04, HL51173, HL31197] Funding Source: Medline
- NIDDK NIH HHS [P30 DK54781] Funding Source: Medline
Ask authors/readers for more resources
We investigated the mechanisms of endogenous nitric oxide (NO) modulation of lung sodium (Na+) transport. C57BL/6 mice injected intraperitoneally with the specific inducible NO synthase (NOS) inhibitor 1400W (110 mg/kg every 8 h for 72 h) exhibited decreased alveolar nitrite levels and Na+-dependent amiloride-sensitive alveolar fluid clearance as compared with mice injected with vehicle. Similarly, pretreatment of mouse tracheal epithelial cells with 140OW abolished the inhibitory effects of amiloride on their Na+ short circuit currents. On the other hand, mouse tracheal epithelial cells pretreated with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of guanylate cyclase, had lower levels of cGMP, but normal values of amiloride-sensitive Na+ currents. Amiloride also inhibited whole-cell Na+ currents across A549 cells treated with vehicle (K-i = 249 nM), but had no effect in A549 cells treated with 1400W. Western blotting studies showed significantly lower levels of a and gammaENaC in lung tissues and alveolar type II (ATII) cells from iNOS(-/-) as well as iNOS(+/+) mice treated with 140OW, as compared with the corresponding values from vehicle-treated iNOS(+/+) mice. Similar values for ratios of alpha, beta, and gammaenacto gapdh were obtained by real-time polymerase chain reaction for iNOS(+/+) mice and iNOS(-/-) mice. We concluded that NO derived from NOS under basal conditions is necessary for amiloride-sensitive Na+ transport across lung epithelial cells and modulates the amount of alpha and gammaENaC via post-transcriptional, cGMP-independent mechanisms.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available