Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a diet containing docosahexaenoic acid (DHA)-enriched Euglena glacilis (DHA-Euglena) as the protein source from 5 weeks of age. The effects on endothelial functions were investigated by perfusion experimentation using mesenteric vasculature, and compared with the effects of antihypertensive drugs. (1) At 13 weeks of age, SHRSP fed the DHA-Euglena diet showed an average blood pressure of 220 mmHg, which was 20 mmHg lower (p < 0.05) than that in the control group, while SHRSP of the captopril-treated group (angiotensin I converting enzyme inhibitor: 200 mg/L drinking water) and hydralazine-treated group (vasodilator: 60 mg/L drinking water) showed marked hypotensive effects with blood pressures of 150-160 mmHg and 180-190 mmHg, respectively. (2) The constriction response to norepinephrine (NE) was lower (p < 0.01) in the mesenteric vasculature isolated from the DHA-Euglena-treated SHRSP than in that from the control group. (3) When the mesenteric vasculature isolated from 13-week-old SHRSP fed the DHA-Euglena diet was perfused with an acetylcholine solution (10(-6) M) in the presence of NE (8 x 10(-6) M), the relaxation rate was 81%, which was higher (p < 0.01) than that in the control group (61%). Among the antihypertensive-treated groups, the captopril-treated group gave nearly the same relaxation rate as the DHA-Euglena diet group, while the hydralazine-treated group indicated a slightly lower rate (65%). At 18 weeks of age, the endothelium-dependent relaxation of SHRSP in the control group was further reduced (28%), but in both the DHA-Euglena diet group and antihypertensive-treated groups, the relaxation rates were not substantially different from the levels at 13 weeks of age. Reduction of the endothelium function in SHRSP occurs due to aging and blood pressure elevation. However, by improving nutritional conditions by the feeding of a DHA-Euglena diet, the endothelial functions were protected without a fall in blood pressure unlike antihypertensive drugs. It is hence considered that nutritional improvement helps maintain a sound architecture for the vascular wall, thereby leading to the suppression and delay of onset of cerebrovascular diseases, and subsequently to the prolongation of life-span.