Comparison of the effects of keishibukuryogan and atorvastatin on balloon injury-induced intimal thickening in rat carotid artery

HMG-CoA reductase inhibitors (statins) are frequently used to prevent and/or treat atherosclerosis because of their ability to lower blood cholesterol levels, the most crucial factor affecting atherosclerosis. Recently, keishibukuryogan (KBG), a Kampo medicine, has been reported to prevent atherosclerosis in high cholesterol diet (HCD)-fed rabbits without affecting the blood cholesterol level. Here, we compared the effects of KBG and atorvastatin (ATS) on balloon-induced intimal thickening of the carotid artery in rats fed a normal diet (ND) or an HCD. The inside of each rat carotid artery was denuded using a balloon catheter. ATS or KBG was administered orally to rats, and intimal thickening was assessed histologically two weeks after denudation. Under the ND-fed condition, the intimal thickness of the ATS-treated group was equal to that of the control group, but that of the KBG-treated group was significantly less than that of the control group. On the other hand, both ATS and KBG significantly attenuated intimal thickening under the HCD-fed condition. The serum cholesterol levels of the ATS- and KBG-treated groups were equal to that of the control group under the ND-fed condition. The serum cholesterol level under the HCD-fed condition was not affected by KBG but was slightly lowered by ATS. The malondialdehyde (MDA) content, an index of lipid peroxidation, was significantly increased in the balloon injured-vascular tissue, compared with in non-injured tissue. ATS and KBG did not affect the balloon injury-induced increase in MDA. These results suggest that ATS prevents intimal thickening by lowering the blood cholesterol level in part under hypercholesterolemic condition, whereas KBG prevents intimal thickening regardless of the blood cholesterol level. Oxidative stress is presumed to be at least partly involved in balloon injury-induced intimal thickening. However, neither ATS nor KBG prevented intimal thickening by suppressing oxidative stress.