Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant.
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.
Hotta
N
N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Nakamura
J
J
Sakakibara
F
F
Hamada
Y
Y
Hara
T
T
Mori
K
K
Nakashima
E
E
Sasaki
H
H
Kasama
N
N
Inukai
S
S
Koh
N
N
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
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