title: Hyperoxia/normoxia-driven retinal angiogenesis in mice: a role for angiotensin II.
abstract: OBJECTIVE
  To examine a possible role for the angiotensin system in a rodent model of retinopathy of prematurity.
  
  
  METHODS
  A previously described model was used in which oxygen cycling (5 days hyperoxia and 5 days hypoxia) induced retinal alterations in newborn mice. An angiotensin-converting enzyme inhibitor (perindopril), or angiotensin receptor antagonists AT1 (losartan) or AT2 (PD123319) were administered subcutaneously for 5 days after the hyperoxia exposure. According to histologic methods, the endothelial cell count within the anterior part of the ganglion cell layer was used for the evaluation of the compound effect.
  
  
  RESULTS
  Histologic evaluation showed an increased number of endothelial cells in retinas of hypoxic pups compared with hyperoxic or normoxic pups. Hypoxic animals treated with perindopril (4 mg/kg) showed a significant decrease (29%, P < or = 0.001) in endothelial cell number (163 +/- 7) compared with hypoxic control animals (231 +/- 10). Losartan also decreased the endothelial cell number (14%, P < or = 0.05), whereas the AT2 antagonist had no effect.
  
  
  CONCLUSIONS
  The data showed a protective effect of an angiotensin-converting enzyme inhibitor and of an AT1 receptor antagonist on hyperoxia- and normoxia-induced neovascularization in newborn mice. The results suggest a role for the angiotensin system in this model and that such compounds may be of interest in the prevention of proliferative retinopathies such as proliferative diabetic retinopathy.
authors.affiliation: Division of Diabetes and Metabolic Diseases, Institut de Recherches Servier, Suresnes, France. michel.lonchampt@fr.netgrs.com
authors.forename: M
authors.initials: M
authors.lastname: Lonchampt
authors.forename: L
authors.initials: L
authors.lastname: Pennel
authors.forename: J
authors.initials: J
authors.lastname: Duhault
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D003911:Dextrans / Q000378:metabolism; D004727:Endothelium; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia / Q000150:complications*; D000860:Hypoxia / Q000150:complications*; D007093:Imidazoles / Q000494:pharmacology; D007231:Infant, Newborn; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020913:Perindopril / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000819:agonists; D012084:Renin-Angiotensin System / Q000502:physiology; D012165:Retinal Ganglion Cells; D015861:Retinal Neovascularization / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003911:Dextrans; D005452:Fluoresceins; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C052526:fluorescein-dextran; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan; D020913:Perindopril