Effect of olmesartan on oxidative stress in hypertensive patients. Mechanistic support to clinical trials derived evidence

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 remodeling-related pathways, p22(phox) and HO-1, along with the phosphorylation state of ERK1/2 and plasma oxidized low-density lipoproteins (oxLDL). Twenty untreated essential hypertensive patients (range blood pressure: 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 p22(phox) and HO-1 protein expression, phosphorylation state of ERK1/2 (western blot) and oxLDL level (ELISA) evaluations. 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, analysis of variance: p < 0.001). p22(phox) protein level declined at 3 months (7.10 +/- 2.61 vs 9.32 +/- 2.43 densitometric units (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. These results demonstrate that olmesartan inhibits oxidative stress. Given the involvement of oxidative stress and its signaling in atherogenesis, and the available evidence of olmesartan's vasoprotective, anti-inflammatory and antiatherosclerotic effects derived from clinical trials in humans, 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 antiremodeling effects reported on the clinical ground.