Selective downregulation of ANP-clearance-receptor gene expression in lung of rats adapted to hypoxia.
To test the hypothesis that expression of atrial natriuretic peptide (ANP)-receptor genes is modified to provide a compensatory mechanism against hypoxic pulmonary hypertension, steady state mRNA levels for the ANP-A receptor (or guanylate cyclase-A; ANPAR), ANP-B receptor (or guanylate cyclase-B; ANPBR), and ANP-clearance receptor (ANPCR) were quantitated by Northern blot and slot-blot analysis in lung, kidney, spleen, and liver of hypoxia-adapted rats and air controls. Exposure of rats to short-term (48 h) and chronic (4 wk) hypoxia (10% O2, 1 atm) did not affect lung ANPAR-mRNA levels. Lung ANPBR-mRNA levels were unchanged by short-term hypoxia but selectively increased (approximately twofold) by chronic hypoxia. ANPCR-mRNA levels were selectively and significantly downregulated by 48-h and 4-wk hypoxia in lung but were unchanged or upregulated in other tissues. Lung ANPCR gene transcription, assessed by nuclear-runoff analysis, was decreased by hypoxia. These data support the conclusion that altered pulmonary ANP-receptor gene expression modulates the development of hypoxic pulmonary hypertension.
Li
H
H
Department of Medicine, University of Alabama at Birmingham 35294.
Oparil
S
S
Meng
Q C
QC
Elton
T S
TS
Chen
Y F
YF
D000222:Adaptation, Physiological; D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D000860:Hypoxia / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D013154:Spleen / Q000503:physiopathology
D015335:Molecular Probes; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor