Document Detail


Effect of olmesartan on oxidative stress in hypertensive patients: mechanistic support to clinical trials derived evidence.
MedLine Citation:
PMID:  21504378     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lorenzo A Cal; Lucia Dal Maso; Paola Caielli; Elisa Pagnin; Maria Fusaro; Paul A Davis; Achille C Pessina
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-20
Journal Detail:
Title:  Blood pressure     Volume:  20     ISSN:  1651-1999     ISO Abbreviation:  Blood Press.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-04-02     Revised Date:  2013-08-15    
Medline Journal Info:
Nlm Unique ID:  9301454     Medline TA:  Blood Press     Country:  England    
Other Details:
Languages:  eng     Pagination:  376-82     Citation Subset:  IM    
Affiliation:
Department of Clinical and Experimental Medicine, University of Padova, Italy. renzcalo@unipd.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Antihypertensive Agents / administration & dosage*,  therapeutic use
Antioxidants / administration & dosage*,  therapeutic use
Blood Pressure*
Blotting, Western
Clinical Trials as Topic
Drug Administration Schedule
Enzyme-Linked Immunosorbent Assay
Female
Heme Oxygenase-1 / analysis,  biosynthesis
Humans
Hypertension* / drug therapy,  metabolism,  physiopathology
Imidazoles / administration & dosage*,  therapeutic use
Italy
Leukocytes, Mononuclear / cytology,  drug effects*,  metabolism
Lipoproteins, LDL / blood
Male
Middle Aged
Mitogen-Activated Protein Kinase 1 / analysis,  biosynthesis
Mitogen-Activated Protein Kinase 3 / analysis,  biosynthesis
NADPH Oxidase / analysis,  biosynthesis
Oxidative Stress / drug effects*
Phosphorylation
Tetrazoles / administration & dosage*,  therapeutic use
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Antioxidants; 0/Imidazoles; 0/Lipoproteins, LDL; 0/Tetrazoles; 0/oxidized low density lipoprotein; 6M97XTV3HD/olmesartan medoxomil; EC 1.14.99.3/HMOX1 protein, human; EC 1.14.99.3/Heme Oxygenase-1; EC 1.6.3.1/CYBA protein, human; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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