Abstract Antioxidant protection provided by different doses of α-tocopherol was compared by determining nitric oxide synthase (NOS) activity in blood vessels of spontaneously hypertensive rats (SHR) treated with α-tocopherol. SHR were divided into four groups namely hypertensive control (C), treatment with 17 mg of α-tocopherol/kg diet (α1), 34 mg of α-tocopherol/kg diet (α2), and 170 mg of α-tocopherol/kg diet (α3). Wister Kyoto (WKY) rats were used as normal control (N). Blood pressure were recorded from the tail by physiography every other night for the duration of the study period of 3 months. At the end of the trial, animals were sacrificed. The NOS activity in blood vessels was measured by [ 3H]arginine radioactive assay and the nitrite concentration in plasma by spectrophotometry at wavelength 554 nm using Greiss reagent. Analysis of data was done using Student’s t test and Pearson’s correlation. The computer program Statistica was used for all analysis. Results of our study showed that for all the three α-tocopherol-treated groups, blood pressure was significantly ( P < .001) reduced compared to the hypertensive control and maximum reduction of blood pressure was shown by the dosage of 34 mg of α-tocopherol/kg diet (C: 209.56 ± 8.47 mm Hg; α2: 128.83 ± 17.13 mm Hg). Also, NOS activity in blood vessels of SHR was significantly lower than WKY rats (N: 1.54 ± 0.26 pmol/mg protein, C: 0.87 ± 0.23 pmol/mg protein; P < .001). Although α-tocopherol in doses of α1, α2, and α3 increased the NOS activity in blood vessels, after treatment only that of α2 showed a statistical significance ( P < .01). Plasma nitrite concentration was significantly reduced in SHR compared to normal WKY rats (N: 54.62 ± 2.96 mol/mL, C: 26.24 ± 2.14 mol/mL; P < .001) and accordingly all three groups showed significant improvement in their respective nitrite level ( P < .001). For all groups, NOS activity and nitrite level showed negative correlation with blood pressure. It was significant for NOS activity in hypertensive control (r = −0.735, P = .038), α1 (r = −0.833, P = .001), and α2 (r = −0.899, P = .000) groups. For plasma nitrite, significant correlation was observed only in group α1 (r = −0.673, P = .016) and α2 (r = −0.643, P = .024). Only the α2 group showed significant positive correlation (r = 0.777, P = .003) between NOS activity and nitrite level. In conclusion it was found that compared to WKY rats, SHR have lower NOS activity in blood vessels, which upon treatment with antioxidant α-tocopherol increased the NOS activity and concomitantly reduced the blood pressure. There was correlation of lipid peroxide in blood vessels with NOS and nitric oxide, which implies that free radicals may be involved in the pathogenesis of hypertension.