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...

Sesame peptide powder (SPP) exhibited angiotensin I-converting enzyme (ACE) inhibitory activity, and significantly and temporarily decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) by a single administration (1 and 10 mg/kg). Six peptide ACE inhibitors were isolated and identified from SPP. The representative peptides, Leu-Val-Tyr, Leu-Gln-Pro and Leu-Lys-Tyr, could competitively inhibit ACE activity at respective Ki values of 0.92 microM, 0.50 microM, and 0.48 microM. A reconstituted sesame peptide mixture of Leu-Ser-Ala, Leu-Gln-Pro, Leu-Lys-Tyr, Ile-Val-Tyr, Val-Ile-Tyr, Leu-Val-Tyr, and Met-Leu-Pro-Ala-Tyr according to their content ratio in SPP showed a strong antihypertensive effect on SHR at doses of 3.63 and 36.3 microg/kg, which accounted for more than 70% of the corresponding dosage for the SPP-induced hypotensive effect. Repeated oral administration of SPP also lowered both SBP and the aortic ACE activity in SHR. These results demonstrate that SPP would be a beneficial ingredient for preventing and providing therapy against hypertension and its related diseases.

These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.

SummaryThe purpose of the present study was to examine the effects of dietary supplementation of arachidonic acid (ARA) on age-related changes in endothelium-dependent vascular responses. Young male Fisher-344 rats (2-mo-old) and aged rats of the same strain (22-mo-old) were randomly separated into a control diet group (young control, YC; old control, OC) and an ARA-containing diet group (young ARA, YA; old ARA, OA). After a 2-mo feeding period, vascular responses were evaluated using both endothelium-intact and -denuded aortic rings. Phenylephrine ( ␣ 1 -adrenoceptor agonist)-induced vasoconstrictor responses in endothelium-intact rings from group OC tended to be augmented compared with those of rings from groups YC and YA, although this augmentation was significantly suppressed by dietary supplementation of ARA. There were no significant differences in vascular responses to phenylephrine in endothelium-denuded rings among groups YC, YA, OC, and OA. Acetylcholine (Ach)-induced, endothelium-dependent vasorelaxation was attenuated in groups OC and OA compared with that in groups YC and YA. ARA supplementation induced slight enhancement of Ach-induced vasorelaxation in aged rats. Ach-induced vasorelaxation correlated very well with aortic ARA concentration in aged rats, but not in young rats. There were no significant differences in endothelium-independent vasodilator responses to sodium nitroprusside in endothelium-denuded rings among groups YC, YA, OC, and OA. These findings suggest that dietary ARA supplementation improves the age-related endothelial dysfunction that leads to various cardiovascular diseases. Key Words aging, arachidonic acid, endothelial dysfunction, acetylcholine, phenylephrine Age is a recognized independent risk factor for the development of cardiovascular disease. There is accumulating evidence in both humans and experimental animals that aging is associated with endothelial dysfunction characterized by progressive decline in endothelium-dependent vasorelaxation in resistance and conductance arteries ( 1-3 ). Although the mechanisms underlying this age-related endothelial dysfunction are not fully understood, several factors, including attenuation of nitric oxide (NO)-mediated vasodilation, augmented production of oxygen-derived free radicals, and increased release of cyclooxygenase-derived vasoconstrictor substances, appear to contribute to this vascular change ( 4 ).Arachidonic acid (ARA) is a major constituent of cell membranes, and in this capacity plays important roles in the maintenance of physiological function. Several studies have demonstrated that the amount of ARA in membrane phospholipids in the brain is lower in aged animals than in young animals, and that certain neural deficiencies in aged animals are closely related to this decrease in membrane ARA concentration ( 5, 6 ). It has recently been reported that dietary ARA supplementation to aged rats can alleviate age-related neural dysfunction ( 7 , 8 ).However, little is known concerning the involvement of membrane ARA in age-...

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