Kallidinogenase normalizes retinal vasopermeability in streptozotocin-induced diabetic rats: potential roles of vascular endothelial growth factor and nitric oxide.
We studied the suppressant effect of kallidinogenase on retinal vascular permeability and vascular endothelial growth factor (VEGF) in diabetic rats. Diabetes was induced by intravenously injecting streptozotocin (60 mg/kg body weight) dissolved in citrate buffer. Kallidinogenase (7 microg/kg/day) was injected intravenously once daily for 21 days. The retinal vascular permeability was estimated from the amount of fluorescent dye leaking into the retina after administration of fluorescein isothiocyanate-conjugated dextran. VEGF in intraocular fluids was quantified by an enzyme-linked immunosorbent assay. The amounts of nitrite and nitrate in the retina were quantified by a fluorescence method using 2,3-diaminonaphthalene. Retinal vascular permeability in the diabetic control group was about 5.5 times higher than in the normal control group (P<0.001). Kallidinogenase suppressed the increased retinal vascular permeability. In the diabetic control group, the VEGF level was three times that of the normal control group (diabetic control group, 160+/-12 pg/ml; normal control group, 54+/-9 pg/ml; P<0.001). The VEGF concentration in the kallidinogenase-treated group was 120+/-12 pg/ml (P<0.05). In the diabetic control group, the amounts of nitrite and nitrate in the retina were lower by about 2.6-fold, compared with the normal control group (P<0.05). Kallidinogenase almost normalized the decreases in nitrite and nitrate in the retina. The current study showed beneficial effects of kallidinogenase on increased retinal vascular permeability and VEGF in diabetic rats, suggesting that kallidinogenase may be effective for simple retinopathy in patients with diabetes.
Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Co, Ltd, Mie, Japan. no_katoh@mb4.skk-net.com
Noriaki
N
Kato
Yunlong
Y
Hou
Zhenhui
Z
Lu
Chunmei
C
Lu
Hiroshi
H
Nagano
Kiyoshi
K
Suzuma
Hitoshi
H
Takagi
Yukiharu
Y
Matsumoto
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000201:enzymology; D006442:Glycated Hemoglobin / Q000378:metabolism; D007610:Kallikreins / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007610:Kallikreins; D009569:Nitric Oxide; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A