The effect of sorbinil, an aldose reductase inhibitor, on aortic function in control and streptozotocin-induced diabetic rats.
1. The present study investigates the effect of treatment of 14-day streptozotocin-diabetic rats with the aldose reductase inhibitor, sorbinil, on changes ex vivo in aortic vasoconstriction and vasodilation. 2. Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in aortae from 14-day diabetic rats, in accordance with our previous data. 3. Endothelium-dependent relaxations to carbachol were, in contrast, depressed, although endothelium-independent relaxations to forskolin and sodium nitroprusside were unaltered. 4. Sorbinil treatment of diabetic animals failed to prevent any of these diabetes-induced alterations in aortic function, and indeed exacerbated some of these alterations. In addition, sorbinil treatment caused altered aortic responses in control animals, which sometimes mirrored those found in diabetic animals. 5. It can be concluded that sorbinil may have actions in addition to, and independent of, polyol pathway inhibition. Thus, sorbinil may not be an effective tool for the investigation of aldose reductase inhibition within the vascular system of the rat.
Sellers
D J
DJ
Department of Biomedical Science, University of Sheffield, Western Bank, UK.
Chess-Williams
R
R
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000449:Aldehyde Reductase; C026411:sorbinil