Hypoxia decreases atrial natriuretic peptide clearance receptor gene expression in pulmonary vascular smooth muscle cells in situ

Academic Article


  • We previously demonstrated that rats exposed to hypoxia exhibit increased circulating atrial natriuretic peptide (ANP) levels. Whether this is related to increased synthesis and/or decreased clearance of ANP is unclear. The current study investigated the effects of hypoxia on the cellular localization and/or steady state levels of ANP clearance receptor gene transcripts (ANP-CR mRNA) in rat lung. Sprague-Dawley rats were exposed to hypoxia (10% O2, 1 atm) for 48 hrs. Lung sections from 5 hypoxia-adapted and 5 air control rats were examined by in situ hybridization using a selective rat ANP-CR 33P-cRNA probe. A total of 819 vessels on 85 lung sections 98-10 sections/rat, 5 rats/group) were analyzed. Analyses were carried out by a single examiner, who was blinded with respect to the group to which each section belonged. Results [meanĀ±SEM, % (positive/total) vessels scanned]: Air control Hypoxia ANP-CR mRNA 21.2% (99/468) 0.6% (2/351) These data indicate that hypoxic exposure is associated with down-regulated expression of ANP-CR in vascular smooth muscle cells in lung. These findings support the hypothesis that altered pulmonary ANP-CR gene expression in vascular smooth muscle cells modulates the development of hypoxic pulmonary hypertension by reducing clearance of circulating ANP.
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    Author List

  • Sun SD; Durand J; Chen YF; Oparil S
  • Volume

  • 44
  • Issue

  • 1