plastochromanol-8 and Hypertension

Involvement of free radicals and nitric oxide (NO) has long been implicated to the pathogenesis of essential hypertension. Several studies using antioxidants as the radical scavenger have shown to confer protection against free radical mediated diseases. This study is designed to investigate the role of antioxidant gamma-tocotrienol on endothelial nitric oxide synthase (NOS) activity in spontaneously hypertensive rats (SHR). SHR's were divided into four groups namely untreated SHR (HC), treatment with 15 mg gamma-tocotrienol/kg diet (gammal), 30 mg gamma-tocotrienol/kg diet (gamma2) and 150 mg gamma-tocotrienol/kg diet (gamma3) and studied for three months. Wister Kyoto (WKY) rats were used as the control (C). Blood pressure was recorded every fortnightly by tail plethysmography. Animals were sacrificed and NOS activity in blood vessels was measured by [3H]arginine radioactive assay. Nitrite concentration in plasma was determined by Greis assay and lipid peroxides in the blood vessels by spectrofluorometry. This study showed that gamma-tocotrienol significantly reduced systolic blood pressure (SBP) in SHRs with a maximum reduction in group treated with gamma-tocotrienol 15 mg/kg diet (HC: 210 +/- 9 mmHg, gammal:123 +/- 19 mmHg). Blood vessels from untreated SHR showed a reduced NOS activity compare to that of WKY rats (C: 1.54 +/- 0.26 pmol/mg protein, HC: 0.87 +/- 0.23 pmol/mg protein; p<0.001). Gamma-tocotrienol improves NOS activity in all the groups with more significance in group gamma2 (p<0.001) and gamma3 (p<0.05). Plasma level of nitrite was reduced in SHR from 55 +/- 3 microM/ml in WKY to 26+/-2 muM/ml (p<0.001). Plasma nitrite level was reversed by treatment with gamma-tocotrienol. (gammal: p<0.001, gamma2: p<0.005, gamma3: p<0.001, respectively). In all the treatment groups, NOS activity showed significant negative correlation with blood pressure (gammal: r=-0.716, p<0.05; gamma2: r=-0.709, p<0.05; gamma3: r=-0.789, p<0.05). For plasma nitrite, although it shows a negative correlation with blood pressure it was significant only in gammal (r=-0.676, p<0.05) and gamma2 (r=-0.721, p<0.05). From this study we found that compared to WKY rats, SHR has lower NOS activity in blood vessels, which upon treatment with antioxidant gamma-tocotrienol increased the NO activity and concomitantly reduced the blood pressure. These findings further strengthen the hypothesis that free radicals and NO play critical role in pathogenesis of essential hypertension.

Topics: Administration, Oral; Aging; Animals; Antioxidants; Blood Pressure; Blood Vessels; Chromans; Dose-Response Relationship, Drug; Hypertension; Lipid Peroxides; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitrites; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Systole; Time Factors; Vitamin E

The aim of this study was to determine the effects of gamma tocotrienol 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 gamma tocotrienol (gamma1, 15 mg/kg diet; gamma2, 30 mg/kg diet and gamma3, 150 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressure were recorded every fortnightly for three 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 were carried out following well established methods. Study shows that lipid peroxides were significantly higher in hypertensive plasma and blood vessels compared to that of normal rats (Plasma- N: 0.06+/-0.01, HC: 0.13+/-0.008; p<0.001, B1. Vessels - N: 0.47+/-0.17, HC: 0.96+/-0.37; p<0.001). SOD activity was significantly lower in hypertensive than normal rats (N = 148.58+/-29.56 U/ml, HC = 110.08+/-14.36 U/ml; p = 0.014). After three months of antioxidant trial with gamma-tocotrienol, it was found that all the treated groups have reduced plasma lipid peroxides concentration but was only significant for group gamma1 (gamma1: 0.109+/-0.026, HC: 0.132+/-0.008; p = 0.034). On the other hand, lipid peroxides in blood vessels reduced significantly in all treated groups (gamma1; p<0.05, gamma2; p<0.001, gamma3; p<0.005). All the three treated groups showed improve total antioxidant status (p<0.001) significantly. SOD activity also showed significant improvement in all groups (gamma1: p<0.001, gamma2: p<0.05, gamma3: p<0.001). Correlation studies showed that, total antioxidant status (TAS) and SOD were significantly negatively correlated with blood pressure in normal rats (p = 0.007; p = 0.008) but not in SHR control. This correlation regained in all three groups SHR's after treatment with tocotrienol. Lipid peroxides in blood vessel and plasma showed a positive correlation with blood pressure in normal and SHR control. This correlation also remains in treated groups significantly except that in gamma3 where positive correlation with plasma lipid peroxide was not significant. In conclusion it was found that antioxidant supplement of gamma-tocotrienol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessel

Topics: Animals; Antioxidants; Blood Pressure; Chromans; Hypertension; Lipid Peroxidation; Lipid Peroxides; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxide Dismutase; Treatment Outcome; Vitamin E