Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells.

Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO(2)<40 torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to normoxic (pO(2) ~100 torr) conditions. PAF binding was quantified in fmol/10(6) cells (mean ± SEM). PAF binding in normoxia were SMC-PA, 5.2 ± 0.2 and in SMC-PV, 19.3 ± 1.1; values in acute hypoxia were SMC-PA, 7.7 ± 0.4 and in SMC-PV, 27.8 ± 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA, but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV, respectively. During normoxia, PAFr mRNA expression by both cell types was similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia after 48 h hypoxia decreased binding by 45-60%, suggesting immediate down-regulation of hypoxia-induced PAFr-mediated effects. We speculate that re-oxygenation immediately reverses hypoxia effect probably due to oxygen tension-dependent reversibility of PAFr activation and suggest that exposure of the neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the neonatal lungs.
AuthorsLissette S Renteria, J Usha Raj, Basil O Ibe
JournalMolecular genetics and metabolism (Mol Genet Metab) Vol. 101 Issue 4 Pg. 400-8 (Dec 2010) ISSN: 1096-7206 [Electronic] United States
PMID20813571 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Inositol Phosphates
  • Platelet Activating Factor
  • Platelet Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • Oxygen
  • Calcium
  • Animals
  • Anoxia (genetics, metabolism)
  • Calcium (metabolism)
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Fetus
  • Inositol Phosphates (metabolism)
  • Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
  • Oxygen (metabolism, pharmacology)
  • Platelet Activating Factor (pharmacology)
  • Platelet Membrane Glycoproteins (biosynthesis, genetics, metabolism)
  • Pregnancy
  • Pulmonary Artery (cytology, metabolism)
  • Pulmonary Veins (cytology, metabolism)
  • RNA, Messenger (biosynthesis, genetics)
  • Receptors, G-Protein-Coupled (biosynthesis, genetics, metabolism)
  • Sheep

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