Acute probucol treatment partially restores vasomotor activity and abnormal lipid metabolism whereas morphological changes are not affected in aorta from long-term STZ-diabetic rats.
The effects of acute probucol treatment on plasma lipids, lipid peroxides and vasomotor activity and structure of aorta were investigated in long-term streptozotocin (STZ)-diabetic rats. Treatment with probucol (300 mg/kg/day, i.o.) was initiated 10 weeks after the induction of diabetes and was continued for 2 or 3 weeks. Plasma cholesterol, triglyceride and thiobarbituric acid reactive substance (TBARS) levels were markedly increased in untreated diabetic rats, however, probucol treatment led to significant reductions in all of these characteristics in diabetic animals. Plasma glucose and insulin levels were similar between untreated and probucol-treated diabetic groups. STZ-diabetes impaired morphological integrity of aorta and caused significantly increase in contractile response to noradrenaline (NA). The percentage of endothelial response (PER), which was calculated in terms of the NA-induced maximum contractile response of aorta, as index of endothelial function, significantly decreased in untreated diabetic rats. Treatment of diabetic rats with probucol resulted in partial restorations in endothelial function and NA-induced contraction in aorta, whereas morphological changes were not affected. These observations suggest that the ability of acute probucol treatment to restore vessel functions may have important implications regarding the pathogenesis and treatment of diabetes and its complications.
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Turkey. karasu@pharmacy.ankara.edu.tr
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D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D008854:Microscopy, Electron; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011341:Probucol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
D000924:Anticholesteremic Agents; D007328:Insulin; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D002784:Cholesterol; D011341:Probucol