alpha-tocopherol increased nitric oxide synthase activity in blood vesselsof spontaneously hypertensive rats

Antioxidant protection provided by different doses of a-tocopherol was comp ared by determining nitric oxide synthase (NOS) activity in blood vessels o f spontaneously hypertensive rats (SHR) treated with alpha-tocopherol. SHR were divided into four groups namely hypertensive control (C), treatmen t with 17 mg of alpha-tocopherol/kg diet (alpha 1), 34 mg of alpha-tocopher ol/kg diet (alpha 2), and 170 mg of alpha-tocopherol/kg diet (alpha 3). Wis ter Kyoto (WKY) rats were used as normal control (N). Blood pressure were r ecorded 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 sacrif iced. The NOS activity in blood vessels was measured by [H-3]arginine radio active assay and the nitrite concentration in plasma by spectrophotometry a t 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 th e 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; alpha 2: 128.83 +/- 17.13 mm Hg). Also, NOS activity in blood vessels of S HR 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 alpha 1, alpha 2, and alpha 3 increased the NOS activity in blood vessels, after treatment only that of alpha 2 showed a statistical signific ance (P < .01). Plasma nitrite concentration was significantly reduced in S HR 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 impr ovement in their respective nitrite level (P < .001). For all groups, NOS a ctivity and nitrite level showed negative correlation with blood pressure. It was significant for NOS activity in hypertensive control (r = -0.735, P = .038), alpha 1 (r = -0.833, P = .001), and alpha 2 (r = -0.899, P = .000) groups. For plasma nitrite, significant correlation was observed only in g roup alpha 1 (r = -0.673, P = .016) and alpha 2 (r = -0.643, P = .024). Onl y the alpha 2 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 ac tivity in blood vessels, which upon treatment with antioxidant alpha-tocoph erol increased the NOS activity and concomitantly reduced the blood pressur e. There was correlation of lipid peroxide in blood vessels with NOS and ni tric oxide, which implies that free radicals may be involved in the pathoge nesis of hypertension. (C) 1999 American Journal of Hypertension, Ltd.