The antihypertensive effect of sesamin, a lignan from sesame oil, was examined using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats (SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking water. Each group was further divided into two groups: normal-diet group and sesamin-diet group. Systolic blood pressure of all animals was monitored once weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal damage were evaluated. In the salt-loaded group, sesamin feeding significantly suppressed the development of hypertension, and efficient suppression was maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old). The left ventricle plus septum weight-to-body weight ratio was slightly but significantly lowered by sesamin feeding. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, wall thickness and wall area of these vessels were significantly decreased by the sesamin feeding. Histological renal damage such as thickening of the tunica intima and fibrinoid degeneration of the arterial wall were often observed in the normal-diet group, but this damage was efficiently reduced in the sesamin-fed animals. On the other hand, in the salt-unloaded group, only a slight and nonsignificant suppressive effect of sesamin on the development of hypertension was observed. Although the wall area of the aorta was significantly decreased by the sesamin feeding, other vascular parameters were not ameliorated. The incidence of histological renal damage tended to decrease in sesamin-fed animals, but these alterations were not statistically significant. Thus, sesamin feeding was much more effective as an antihypertensive regimen in salt-loaded SHRSP than in unloaded SHRSP, thereby suggesting that sesamin is more useful as a prophylactic treatment in the malignant status of hypertension and/or hypertension followed by water and salt retention.