Oxidative stress is involved in the initiation and progression of atherosclerosis. Oxygen free radicals either on cell wall membrane or on LDL particles facilitate lipid peroxidation nonenzymatically in several clinical conditions related to oxidative stress such as aging, smoking, coronary ischemia-reperfusion and diabetes mellitus. We examined the antioxidant activities of thiazolidinediones (insulin sensitizer) and their effect on cardiovascular function in type 2 diabetic model rats, and also those of dihydropyridines (commonly used anti-anginal and antihypertensive agents) in cultured human endothelial cells. In the pre-diabetic or early diabetic stage, hyperinsulinemia or insulin resistance is thought to be closely associated with oxidative stress. We administered pioglitazone or troglitazone, and measured 8-iso-prostagalandin F_2α and malondi aldehyde-thiobarbituricacid. This study demonstrated impairment of the antioxidative system and an accumulation of collagen in the myocardium or aortic wall, and confirmed the antioxidant effects of thiazolidinedione compounds.
In the present review, we introduce the role of transforming growth factor (TGF)-β-mediating cardiovascular complications and the effects of thiazolidinediones on cardiovascular function. We also examined the effects of dihydropyridine-type calcium antagonists on lipid peroxidation in cultured human arterial endothelial cells. Endothelial cells were exposed to 1mM H₂O₂, and then treated with nifedipine, amlodipine or azelnidipine (a newly developed dihydropyridine). The antioxidant activity was evaluated by measuring 8-iso-prostaglandine F_2α concentration. Azelnidipine exhibits potent antioxidant activities, which we also introduced in this review.