Abstract
A close relationship between the renin-angiotensin system and the pathophysiology of diabetic retinopathy has been suggested, several angiotensin II type 1 receptor (angiotensin AT1 receptor) antagonists being effective in animal models. Therefore, we examined the efficacy of an angiotensin AT1 receptor antagonist, olmesartan medoxomil (CS-866), in animal retinopathy models. In diabetic stroke-prone spontaneously hypertensive (SHRSP) rats, 4-week treatment with CS-866 prevented the elongation of oscillatory potential peaks dose-dependently which almost normalized at 3 mg/kg/day. Next, in oxygen-induced retinopathy mice, CS-866 at 1 mg/kg significantly prevented the retinal neovascularization. In these animal models, plasma concentrations of CS-866 were comparable to the in vitro IC50 value of the angiotensin AT1 receptor. In summary, our data demonstrated that CS-866 was effective in early and late stage retinopathy models through the inhibition of the angiotensin AT1 receptor. These findings suggest the possibility of CS-866 as a therapeutic agent for diabetic retinopathy.
MeSH terms
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Angiotensin II Type 1 Receptor Blockers / pharmacokinetics
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Angiotensin II Type 1 Receptor Blockers / pharmacology*
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Animals
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Area Under Curve
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Benzimidazoles / pharmacokinetics
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Benzimidazoles / pharmacology
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Biphenyl Compounds / pharmacokinetics
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Biphenyl Compounds / pharmacology
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Blood Glucose / metabolism
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Blood Pressure / drug effects
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Body Weight / drug effects
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Experimental / physiopathology
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Diabetic Retinopathy / blood
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Diabetic Retinopathy / physiopathology
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Diabetic Retinopathy / prevention & control*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Electroretinography
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Glycated Hemoglobin / metabolism
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Heart Rate / drug effects
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Hypertension / complications
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Hypertension / physiopathology
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Hypoxia / physiopathology
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Imidazoles / pharmacokinetics
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Imidazoles / pharmacology*
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Male
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Olmesartan Medoxomil
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Oxygen / pharmacology
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Rats
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Rats, Inbred SHR
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Retinal Neovascularization / metabolism
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Retinal Neovascularization / physiopathology
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Retinal Neovascularization / prevention & control
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Tetrazoles / pharmacokinetics
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Tetrazoles / pharmacology*
Substances
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Angiotensin II Type 1 Receptor Blockers
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Benzimidazoles
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Biphenyl Compounds
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Blood Glucose
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Glycated Hemoglobin A
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Imidazoles
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Tetrazoles
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Olmesartan Medoxomil
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olmesartan
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candesartan cilexetil
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Oxygen