| Effect of olmesartan on oxidative stress in hypertensive patients. Mechanistic support to clinical trials derived evidence. | |
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MedLine Citation:
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PMID: 21504378 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Lorenzo A Calò; Lucia Dal Maso; Paola Caielli; Elisa Pagnin; Maria Fusaro; Paul A Davis; Achille C Pessina |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-20 |
Journal Detail:
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Title: Blood pressure Volume: - ISSN: 1651-1999 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9301454 Medline TA: Blood Press Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Clinical and Experimental Medicine,University of Padova, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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