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Antihypertensive action of TF-80, an alpha-tocopheryl ester of fusaric acid (FA), was studied in normotensive and hypertensive rats. Oral doses of TF-80 up to 100 mg/kg did not affect systolic blood pressure in Wistar rats, whereas 50 and 100 mg/kg doses produced a significant reduction in systolic blood pressure in both spontaneously hypertensive rats (SHR) and DOCA-salt hypertensive rats (DSR) without significant changes in heart rate. Although maximal reduction in systolic blood pressure at single oral dosing of TF-80 (50, 100 mg/kg) and FA (15, 30 mg/kg) was approximately the same extent, respectively, the antihypertensive action of TF-80 was longer-lasting than that of FA. TF-80 at a chronic administration of 1 to 100 mg/kg/day for 6-9 weeks was preventive to the generation of hypertension in young SHR and DSR, but FA did not prevent the generation of hypertension. Hypotensive doses of TF-80 did not interfere in the rise in blood pressure produced by vasoactive substances such as norepinephrine, prostaglandin F2 alpha and angiotensin II in SHR, and it also failed to inhibit plasma renin. TF-80 was also found not to have a diuretic effect. These results show that TF-80 has a mild and long-lasting antihypertensive action that is different from FA. However, the antihypertensive mechanism of TF-80 remains to be solved.

Antihypertensive action of dl-.ALPHA.-tocopherol 5-n-butyl-2-pyridinecarboxylate (TF-80).