Antioxidant protection provided by different doses of alpha-tocopherol was compared by determining nitric oxide synthase (NOS) activity in blood vessels of spontaneously hypertensive rats (SHR) treated with alpha-tocopherol. SHR were divided into four groups namely hypertensive control (C), treatment with 17 mg of alpha-tocopherol/kg diet (alpha1), 34 mg of alpha-tocopherol/kg diet (alpha2), and 170 mg of alpha-tocopherol/kg diet (alpha3). 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 alpha-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 alpha-tocopherol/kg diet (C: 209.56 +/- 8.47 mm Hg; alpha2: 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 alpha-tocopherol in doses of alpha1, alpha2, and alpha3 increased the NOS activity in blood vessels, after treatment only that of alpha2 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), alpha1 (r = -0.833, P = .001), and alpha2 (r = -0.899, P = .000) groups. For plasma nitrite, significant correlation was observed only in group alpha1 (r = -0.673, P = .016) and alpha2 (r = -0.643, P = .024). Only the alpha2 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 alpha-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.

The aim of this study was to determine the effects of alpha-tocopherol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar-Kyoto (WKY) rats. SHR were divided into three groups and treated with different doses of alpha-tocopherol (alpha1, 17 mg/kg diet; alpha2, 34 mg/kg diet; and alpha3, 170 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressures were recorded every 10 days for 3 months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity, and lipid peroxide levels in plasma and blood vessels was carried out following well-established methods. From our study it was found that lipid peroxides in thoracic aorta (N, 0.47 +/- 0.17; H, 0.96 +/- 0.37; P < .0001) and plasma (N, 0.06 +/- 0.01; H, 0.13 +/- 0.01) were significantly higher in hypertensives than in normal rats. SOD activity was significantly lower in hypertensive than normal rats (N, 172.93 +/- 46.91; H, 110.08 +/- 14.38; P < .005). Total antioxidant status was significantly higher in normal than hypertensive rats (N, 0.88 +/- 0.05; H, 0.83 +/- 0.02; P < .05). After the antioxidant trial, it was found that in the treated groups rise of blood pressure was prevented significantly (P < .001) and lipid peroxides in blood vessels were significantly reduced more than in the controls (P < .001). For plasma lipid peroxide it was only significant for groups alpha2 (P < .001) and alpha3 (P < .05). Although all three treated groups showed improved total antioxidant status, only groups alpha2 (0.87 +/- 0.04, P < .005) and alpha3 (1.20 +/- 0.18, P < .001) were statistically significant. All the three groups showed significant increases in their SOD activity (P < .001). Correlation studies showed that total antioxidant status and SOD were significantly negatively correlated with blood pressure in normal rats (P = .007; P = .008). Lipid peroxides in both blood vessel and plasma showed a positive correlation. In the treated groups, lipid peroxides in blood vessels maintained a significant positive correlation with blood pressure in all groups (alpha1, P = .021; alpha2, P = .019; alpha3, P = .002), whereas for plasma lipid peroxides the correlation was in groups alpha1 (P = .005) and alpha2 (P = .009). For SOD activity, significant negative correlations were found with blood pressure in the alpha2 (P = .017) and alpha3 (P = .025) groups. Total antioxidant status maintained a significant negative correlation with blood pressure in all three groups (alpha1, P = .012; alpha2, P = .044; alpha3, P = .014). In conclusion it was found that supplement of alpha-tocopherol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels, and enhance the total antioxidant status, including SOD activity.

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These findings indicate that not only a defect in the nitric oxide pathway, but also a loss of EDHF-mediated responses may be responsible for impaired vasodilation in the aging kidney. This may result in enhanced vasoconstrictive responses in aging which potentially will cause renal damage and ultimately a loss in glomerular filtration rate (GFR).

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