title: Hypoxia-induced relaxation of porcine retinal arterioles in vitro depends on inducible NO synthase and EP4 receptor stimulation in the perivascular retina.
abstract: OBJECTIVE
  Hypoxia-induced relaxation of porcine retinal arterioles has been shown to be reduced during inhibition of prostaglandin synthesis and nitric oxide synthase (NOS). The purpose of this study was to identity the specific prostaglandin receptor(s) and source(s) of NO mediating this effect.
  
  
  METHODS
  Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph and were exposed to hypoxia in the presence of one of the following: the general NO synthase inhibitor L-NAME, the selective iNOS inhibitor 1400W, the selective nNOS inhibitor 7-nitroindazole, the general cyclooxygenase (COX) inhibitor ibuprofen or an antagonist to the FP- (AL 8810), DP- (BWA868C), EP1 - (SC-19220), EP2 - (PF-044189) or EP4 receptors (GW627368X). The experiments were repeated after removal of the perivascular retinal tissue.
  
  
  RESULTS
  Hypoxia induced relaxation of retinal arterioles with preserved perivascular retinal tissue. This relaxation was significantly reduced in the presence of L-NAME, 1400W, ibuprofen and the EP4 receptor antagonist GW627368X. The simultaneous addition of L-NAME or 1400W in combination with ibuprofen, but not GW627368X, reduced hypoxia-induced vasorelaxation additively as compared to the effect of the compounds individually.
  
  
  CONCLUSIONS
  Hypoxia-induced vasorelaxation of porcine retinal arterioles is mediated by inducible NOS and stimulation of EP4 receptors acting through separate pathways, but mechanisms unrelated to the studied prostaglandin receptors and NOS products are also involved.
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Oversø Hansen
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Sidse
authors.initials: S
authors.lastname: Kringelholt
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Ulf
authors.initials: U
authors.lastname: Simonsen
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Toke
authors.initials: T
authors.lastname: Bek
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009213:Myography; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012161:Retinal Artery / Q000502:physiology*; D034421:Sus scrofa
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D058309:Receptors, Prostaglandin E, EP4 Subtype; D052247:Nitric Oxide Synthase Type II
keywords: in vitro experiments; nitric oxide; porcine retinal arterioles; prostaglandins; retinal hypoxia