title: Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant.
abstract: To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.
authors.affiliation: Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hotta
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
authors.forename: F
authors.initials: F
authors.lastname: Sakakibara
authors.forename: Y
authors.initials: Y
authors.lastname: Hamada
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: E
authors.initials: E
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: N
authors.initials: N
authors.lastname: Kasama
authors.forename: S
authors.initials: S
authors.lastname: Inukai
authors.forename: N
authors.initials: N
authors.lastname: Koh
mesh_terms: D019794:2,3-Diphosphoglycerate / Q000378:metabolism; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D019422:Dietary Sucrose / Q000494:pharmacology*; D004596:Electroretinography / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005632:Fructose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D000925:Anticoagulants; D001786:Blood Glucose; D019422:Dietary Sucrose; D004791:Enzyme Inhibitors; D007328:Insulin; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D013876:Thiophenes; D014280:Triglycerides; C080974:(5-(3-thienyl)tetrazol-1-yl)acetic acid; D019794:2,3-Diphosphoglycerate; D005632:Fructose; D013012:Sorbitol; D000449:Aldehyde Reductase; D000077407:Cilostazol