Sesamin is one of the lignans contained abundantly in sesame oil. Previous studies have indicated that sesamin inhibits lipid metabolism, such as desaturation in polyunsaturated fatty acid biosynthesis 1) and cholesterol absorption. 2) In recent studies, we have demonstrated the antihypertensive effect of sesamin using several types of experimental hypertensive models. [3][4][5] The most efficient antihypertensive activity was observed in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat model. Moreover, a development of cardiovascular hypertrophy in these animals was attenuated by the sesamin-feeding. 3)There is accumulating evidence indicating that an oxidative stress in vascular tissues is closely related to the development of hypertensive diseases. 6) Nakazono et al. 7) have shown that blood pressure of spontaneously hypertensive rats (SHR) was decreased markedly by administration of heparinbinding superoxide dismutase (SOD) which bound to vascular endothelial cells. In angiotensin II-induced hypertensive rats, both the development of hypertension and the altered endothelium-dependent vascular relaxation were improved by the treatment with membrane-targeted forms of SOD. 8)These findings suggest that vascular superoxide (O 2 Ϫ ) production is increased in several animal models of hypertension and contributes to the development and/or maintenance of their high blood pressure and endothelial dysfunction.Most recently, we noted that the increased vascular O 2 Ϫ production in DOCA-salt hypertensive animals was normalized almost completely by the feeding of sesamin-containing diet. 9) On the other hand, a previous in vitro study has shown that stretching vascular smooth muscle cells results in increased O 2 Ϫ production, 10) thereby suggesting that the high blood pressure by itself may increase the vascular O 2 Ϫ production. Therefore the possibility that dietary sesamin-induced decreases in vascular O 2 Ϫ production may result from a decrease in blood pressure cannot be ruled out. Thus in the present study, we further evaluated the relationship between the antihypertensive effect of sesamin and its antioxidative activity in DOCA-salt hypertensive rats. MATERIALS AND METHODSMaterials Sesamin was prepared from refined sesame oil and purified as described previously.11) Sesamin-containing diets (0.1, 1 w/w% in commercial normal diet, NMF) were obtained from Oriental Yeast Co., Ltd. (Tokyo, Japan). Reserpine and hydralazine hydrochloride were purchased from Tokyo Kasei Kogyo Co. (Tokyo, Japan). All other reagents used were obtained from Sigma Chemical Co. (St. Louis, Missouri, U.S.A.) and Nacalai Tesque (Kyoto, Japan).Animal Experiments Male Sprague-Dawley rats (6 weeks old) (SLC, Inc., Hamamatsu, Japan), were anesthetized with sodium pentobarbital (40 mg/kg, i.p.), and the right kidney was removed via a right flank incision. After a 1-week postsurgical recovery period, rats were separated into a sham-operated group and a DOCA-salt group. Each group was further divided into five groups: i) normal diet gro...

We previously demonstrated the preventive effect of sesamin, a lignan from sesame oil, on the development of several experimental models of hypertension. In the present study, we explored the mechanisms underlying the antihypertensive effect of sesamin using the deoxycorticosterone acetate (DOCA)-salt rat hypertensive model. After a 5-week treatment period, aortic superoxide (O 2 ؊ ) production was measured in the lucigenin chemiluminescence assay. Chemiluminescence signals significantly decreased in sesamin-containing diet-fed DOCA-salt hypertensive rats compared with those in the normal diet-fed DOCA-salt rats, although the signals in sham-operated control animals were not affected by the sesamin feeding. In addition, there was a positive correlation between systolic blood pressure and aortic O 2 ؊ production. These findings suggest that sesamin feeding inhibits enhanced vascular O 2 ؊ production in DOCA-salt hypertensive rats and that the antioxidative action of sesamin may contribute to its antihypertensive activity. Key words sesamin; deoxycorticosterone acetate (DOCA)-salt hypertension; superoxideWe have demonstrated the antihypertensive effect of sesamin, a lignan from sesame oil, in several types of experimental hypertensive models.1-3) The most efficient activity was observed in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat model. When sesamin-containing diets were fed to the animals, the development of hypertension and cardiovascular hypertrophy were markedly attenuated.1) Most recently, we found that dietary sesamin efficiently improved the diminished endothelium-dependent vasorelaxation in DOCA-salt hypertensive animals. 4) In salt-loaded strokeprone spontaneously hypertensive rats (SHR-SP), sesamin feeding also effectively reduced histologic renal damage such as thickening of the tunica intima and fibrinoid degeneration of the arterial wall, in addition to inhibiting the development of hypertension and cardiovascular hypertrophy. 3)Several studies have been conducted on the biological activities of sesamin and the results have indicated that sesamin inhibits lipid metabolism, such as desaturation in polyunsaturated fatty acid biosynthesis 5) and cholesterol absorption. 6)Furthermore, sesamin is known to exert protective effects against liver damage caused by alcohol or carbon tetrachloride, 7) and against 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinogenesis.8) These effects of sesamin may be due, at least in part, to immunopotentiation and antioxidative activity. production is increased in several animal models of hypertension and that antioxidants, such as vitamin C and vitamin E, attenuate the elevation of blood pressure and the impairment of vascular reactivity in hypertensive animals, 9) although antihypertensive therapy did not always prevent the increased oxidative stress. 10) In the present study, we investigated the possible mechanisms of the antihypertensive effect of sesamin in DOCA-salt hypertensive rats. We hypothesized that sesamin feeding inhibits enhanced v...

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