title: Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture.
abstract: The purpose of the study was to describe endothelin (ET) production and to characterize the effect of hypoxia on preproendothelin-1 (preproET-1) messenger ribonucleic acid (mRNA) expression and ET secretion by rat type II pneumocytes in vitro. Rat type II pneumocytes were incubated in a sealed chamber containing a normoxic (21% O2) or hypoxic (1% O2) atmosphere for increasing durations. Immunoreactive ET (irET) was measured in cell supernatants using a radioimmunoassay. Rat preproET-1 mRNA was detected by Northern blot. Rat type II pneumocytes expressed preproET-1 mRNA, contained irET and secreted irET in a time-dependent manner. ET secretion was dependent on de novo ribonucleic acid (RNA) and protein synthesis. Hypoxia decreased irET secretion by 27% and reduced the steady-state level of preproET-1 mRNA by 60% whereas intracellular irET concentration was unchanged. Inhibition was partially reversible with the return to a normoxic atmosphere. Inhibition of nitric oxide synthesis did not prevent the inhibitory effect of hypoxia. In conclusion, rat type II pneumocytes in primary culture secreted immunoreactive endothelin and expressed preproendothelin-1 messenger ribonucleic acid. Hypoxia reversibly reduced endothelin-1 production through a reduction of the steady-state preproendothelin-1 messenger ribonucleic acid level. Nitric oxide synthesis did not mediate the inhibitory effect of hypoxia.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale INSERM U 408, Faculté Xavier Bichat, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Crestani
authors.forename: C
authors.initials: C
authors.lastname: Odoux
authors.forename: C
authors.initials: C
authors.lastname: Rolland
authors.forename: F
authors.initials: F
authors.lastname: Moldovan
authors.forename: P
authors.initials: P
authors.lastname: Cornillet
authors.forename: J
authors.initials: J
authors.lastname: Fiet
authors.forename: M
authors.initials: M
authors.lastname: Aubier
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D019332:Endothelin-1; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D009569:Nitric Oxide