摘要
Introduction:The role of oxidative stress in the pathophysiology of hypertension and target organ damage is widely recognized.Using a molecular biology approach, we report, in essential hypertensive patients, the effect of the angiotensin II type 1 receptor blocker olmesartan on the mononuclear cell (PBMC) protein expression of major elements in the oxidative stress and vascular remodelling-related pathways, p22phox and HO-1, along with the phosphorylation state of ERK1 2 and plasma oxidized LDL (oxLDL).Methods: Twenty untreated essential hypertensive patients (blood pressure range: 142-156 94-98 mmHg) were treated with olmesartan medoxomil (20 mg day for 6 months) and blood samples collected at baseline, 3 and 6 months for PBMC p22phox and HO-1 protein expression, phosphorylation state of ERK1 2 (western blot) and oxLDL level (ELISA) evaluations.Results: Olmesartan normalized blood pressure since the third month (149 -4.7 94.88 -1.9 mmHg vs 137.89 -2.08 88.44 -2.0 at 3 months and vs 135.44 -2.18 85.78 -1.2 at 6 months, ANOVA: p < 0.001).p22phox protein level declined at 3 months (7.10 -2.61 vs 9.32 -2.43 d.u., p < 0.001), further declining at 6 months (4.55 -1.26 d.u., p < 0.001).HO-1 levels increased at 3 months (10.87 -1.92 vs 7.70 -0.71 d.u., p = 0.001) and remained elevated (11.11 -1.89 d.u., p = 0.001), without further increase at 6 months.Phosphorylated ERK1 2 declined at 3 months (3.94 -1.44 vs 5.62 -1.11 d.u., p = 0.001), further declining at 6 months (1.94 -0.87, p < 0.001).oxLDL significantly declined at 3 and 6 months.Conclusions: These results demonstrate that olmesartan inhibits oxidative stress.Given the involvement of oxidative stress and its signalling in atherogenesis and the available evidence of olmesartan's vasoprotective, anti-inflammatory and antiatherosclerotic effects derived from clinical trials in humans (EUTOPIA, VIOS, MORE and OLIVUS), the results of our study provide a mechanistic rationale for the omelsartan's antioxidant and anti-inflammatory potential translation, in the long term, toward the antiatherosclerotic and antiremodelling effects reported on the clinical ground.