Increased vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozocin-induced diabetes. Prevention by aldose reductase inhibitors and castration.
125I-labeled albumin permeation (IAP) has been assessed in various tissues in spontaneously diabetic insulin-dependent female BB/W rats and in male Sprague-Dawley rats with severe or mild forms of streptozocin-induced diabetes (SS-D and MS-D, respectively). In BB/W diabetic rats and in rats with SS-D, indices of IAP were significantly increased in tissues and vessels predisposed to diabetic vascular disease in humans, including the eyes (anterior uvea, posterior uvea, and retina), sciatic nerve, aorta, kidney, and new vessels formed after induction of diabetes. No evidence of increased IAP was observed in heart, brain, testes, or skeletal muscle in BB/W or SS-D rats. In MS-D rats, indices of IAP were increased only in the kidney and in new vessels formed after the onset of diabetes. Marked tissue differences were observed in the effects of two structurally different aldose reductase inhibitors (sorbinil and tolrestat) and of castration on diabetes-induced increases in IAP and in tissue levels of polyols in SS-D rats. Both aldose reductase inhibitors and castration completely prevented diabetes-induced increases in IAP in new vessels and in sciatic nerve in BB/W and SS-D rats. Both aldose reductase inhibitors also markedly decreased IAP in the anterior uvea (approximately 85%), posterior uvea (approximately 65-75%), retina (approximately 65-70%), and kidney (approximately 70-100%); castration reduced IAP in the anterior uvea (approximately 55%), kidney (approximately 50%), and retina (approximately 30%) but had no effect on the posterior uvea. The diabetes-induced increases in IAP in the aorta were reduced only slightly (approximately 20%) by aldose reductase inhibitors and castration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002199:Capillary Permeability / Q000187:drug effects*; D002369:Castration; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000098:blood supply; D013012:Sorbitol / Q000032:analysis; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D014602:Uvea / Q000098:blood supply
D001786:Blood Glucose; D012739:Gonadal Steroid Hormones; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase