AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 328-L335, Copyright © 1995 by American Physiological Society
Selective downregulation of ANP-clearance-receptor gene expression in lung of rats adapted to hypoxia
H. Li, S. Oparil, Q. C. Meng, T. S. Elton and Y. F. Chen
Department of Medicine, University of Alabama at Birmingham 35294.
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.
