title: Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin II type 1 receptor.
abstract: PURPOSE. To investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II antagonist against retinal ischemia-reperfusion injury in the rat retina. METHODS. Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with an ACE inhibitor (captopril), an angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), an AT2-R antagonist (PD123319), bradykinin, or a bradykinin B2 receptor antagonist (icatibant). At 7 days after the ischemia, retinal damage was evaluated. Immunohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of AT1-R. Dark-adapted full-field electroretinography (ERG) was also performed. RESULTS. Pretreatment with captopril or candesartan significantly inhibited the ischemic injury of the inner retina. However, PD123319, bradykinin, or icatibant did not reduce the ischemic damage. In control retinas, retinal vessels were positive for AT1-R. In contrast, 12 hours after ischemia, immunohistochemical analysis detected numerous AT1-R-positive cells in the inner retina in vehicle-treated rats. After ischemia, the production of ROS was detected in retinal cells. However, pretreatment with captopril or candesartan suppressed the production of ROS. On the seventh postoperative day, the amplitudes of the ERG b-waves were significantly lower in the vehicle group than in the groups pretreated with captopril or candesartan. CONCLUSIONS. The present findings demonstrate that ischemic damage promotes the expression of AT1-R in the inner retina. Both the ACE inhibitor and the AT1-R antagonist that were examined can block the stimulation of the AT1-R and attenuate the subsequent ischemic damage in the rat retina.
authors.affiliation: Departments of Ophthalmology, Kagawa University Faculty of Medicine, Kagawa, Japan. snipeman@med.kagawa-u.ac.jp
authors.forename: Kouki
authors.initials: K
authors.lastname: Fukuda
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirooka
authors.forename: Masanori
authors.initials: M
authors.lastname: Mizote
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Itano
authors.forename: Fumio
authors.initials: F
authors.lastname: Shiraga
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002216:Captopril / Q000494:pharmacology; D002470:Cell Survival; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D018696:Neuroprotective Agents / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D012160:Retina / Q000378:metabolism; D012164:Retinal Diseases / Q000378:metabolism / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D065094:Bradykinin B2 Receptor Antagonists; D007093:Imidazoles; D018696:Neuroprotective Agents; D011725:Pyridines; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C073402:PD 123319; C065679:icatibant; D002216:Captopril; C081643:candesartan; D001920:Bradykinin