Effect of olmesartan on oxidative stress in hypertensive patients. Mechanistic support to clinical trials derived evidence
Lorenzo A. Calò 1, Lucia Dal Maso 1, Paola caielli 1, Elisa Pagnin 1, Maria Fusaro 2, Paul A. Davis 3 & Achille C. Pessina 1
1 Department of Clinical and Experimental Medicine, University of Padova, Italy
2 CNR Aging Section, Institute of Neuroscience, Padova, Italy
3 Department of Nutrition, University of California, Davis, USA
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 signifi cantly 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-infl ammatory 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-infl ammatory potential translation, in the long term, toward the antiatherosclerotic and antiremodeling effects reported on the clinical ground.