Effect of Olmesartan on Oxidative Stress in Hypertensive Patients: Mechanistic Support to Clinical Trials Derived Evidence

Blood Press. 2011 Dec;20(6):376-82. doi: 10.3109/08037051.2011.575570. Epub 2011 Apr 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / therapeutic use
  • Antioxidants / administration & dosage*
  • Antioxidants / therapeutic use
  • Blood Pressure*
  • Blotting, Western
  • Clinical Trials as Topic
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heme Oxygenase-1 / analysis
  • Heme Oxygenase-1 / biosynthesis
  • Humans
  • Hypertension* / drug therapy
  • Hypertension* / metabolism
  • Hypertension* / physiopathology
  • Imidazoles / administration & dosage*
  • Imidazoles / therapeutic use
  • Italy
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Lipoproteins, LDL / blood
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / analysis
  • Mitogen-Activated Protein Kinase 1 / biosynthesis
  • Mitogen-Activated Protein Kinase 3 / analysis
  • Mitogen-Activated Protein Kinase 3 / biosynthesis
  • NADPH Oxidases / analysis
  • NADPH Oxidases / biosynthesis
  • Olmesartan Medoxomil
  • Oxidative Stress / drug effects*
  • Phosphorylation
  • Tetrazoles / administration & dosage*
  • Tetrazoles / therapeutic use

Substances

  • Antihypertensive Agents
  • Antioxidants
  • Imidazoles
  • Lipoproteins, LDL
  • Tetrazoles
  • oxidized low density lipoprotein
  • Olmesartan Medoxomil
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • NADPH Oxidases
  • CYBA protein, human
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3