title: Prostaglandin-mediated inhibition of nitric oxide production by bovine aortic endothelium during hypoxia.
abstract: OBJECTIVE
  The present study utilized a monoculture of vascular endothelium to: (1) determine if nitric oxide (NO) production was decreased during hypoxia, (2) ascertain if specific prostaglandins were released in response to hypoxia, and (3) determine if cyclo-oxygenase inhibition would modulate hypoxia-induced decreases in NO production.
  
  
  METHODS
  Bovine aortic endothelial cells (BAE cells) were grown to confluence on microcarrier beads. NO released in response to the receptor-independent agonist, A23187 calcium ionophore, was directly and continuously measured using a sensitive and specific chemiluminescence method. Cells were exposed to either "hypoxia" (pO2 = 10 mmHg) or "normoxia" (pO2 = 160 mmHg) for 30 min. NO was quantitatively measured with and without indomethacin (1.7 microM) in the incubation medium, and also following incubation with the prostacyclin analog, iloprost. The prostaglandins PGI2 and PGE2 released in response to hypoxia were quantitated using an enzyme immunoassay.
  
  
  RESULTS
  Hypoxia significantly decreased NO production, resulting in a 22.8(2.1)% reduction in NO from 94.3(5.3) nmol/micrograms protein (during normoxia) to 73.5(2) nmol/micrograms protein (during hypoxia). Hypoxia significantly stimulated the production of PGI2 and PGE2, in excess of that released in response to A23187 when compared with normoxia. Following cyclo-oxygenase inhibition, the hypoxia-induced decrease in NO production was abolished (0.13 [2.7] % change relative to controls). Furthermore, iloprost (10 nM) directly inhibited NO production.
  
  
  CONCLUSIONS
  The results demonstrate that ionophore-stimulated NO production is sensitive to oxygen tension, decreasing in response to hypoxia. Inhibition of prostaglandin synthesis restores NO production during hypoxia, while iloprost directly suppresses NO production. Thus, endothelium-derived prostanoids produced in response to hypoxia may modulate NO production via an autocrine negative feedback mechanism.
authors.affiliation: Department of Internal Medicine, University of Missouri, Columbia, USA.
authors.forename: X P
authors.initials: XP
authors.lastname: Xu
authors.forename: M A
authors.initials: MA
authors.lastname: Tanner
authors.forename: P R
authors.initials: PR
authors.lastname: Myers
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005246:Feedback; D000860:Hypoxia / Q000378:metabolism*; D016285:Iloprost / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D007476:Ionophores; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000001:Calcimycin; D011464:Epoprostenol; D016285:Iloprost; D015232:Dinoprostone; D007213:Indomethacin