Document Detail

Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension.
MedLine Citation:
PMID:  19248829     Owner:  NLM     Status:  MEDLINE    
Mounting evidence indicates that structural and functional vascular changes associated with two-kidney, one-clip (2K-1C) hypertension result, at least in part, from altered activity of matrix metalloproteinases (MMPs). Because MMPs are upregulated by increased formation of reactive oxygen species (ROS), we hypothesized that antioxidant approaches could attenuate the increases in MMP-2 expression/activity and the vascular dysfunction and remodeling associated with 2K-1C hypertension. Sham-operated or 2K-1C hypertensive rats were treated with tempol 18 mg/kg/day or apocyanin 25 mg/kg/day (or vehicle). Systolic blood pressure was monitored weekly. After 8 weeks of treatment, aortic rings were isolated to assess endothelium-dependent and -independent relaxation. Quantitative morphometry of structural changes in the aortic wall was studied in hematoxylin/eosin sections. Aortic and systemic ROS levels were measured using dihydroethidine and thiobarbituric acid-reactive substances, respectively. Aortic MMP-2 levels and activity were determined by gelatin and in situ zymography, fluorimetry, and immunohistochemistry. Tempol and apocyanin attenuated 2K-1C hypertension (181+/-20.8 and 192+/-17.6 mm Hg, respectively, versus 213+/-18 mm Hg in hypertensive controls; both p<0.05) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Tempol, but not apocyanin (p>0.05), prevented the vascular remodeling found in 2K-1C rats (all p<0.01). Tempol was more effective than apocyanin in attenuating hypertension-induced increases in oxidative stress (both p<0.05), MMP-2 levels, and MMP-2 activity in hypertensive rats (all p<0.05). Our results suggest that antioxidant approaches decrease MMP-2 upregulation and attenuate the vascular dysfunction and remodeling during 2K-1C hypertension.
Michele M Castro; Elen Rizzi; Gerson J Rodrigues; Carla S Ceron; Lusiane M Bendhack; Raquel F Gerlach; Jose E Tanus-Santos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-25
Journal Detail:
Title:  Free radical biology & medicine     Volume:  46     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-06     Completed Date:  2009-06-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1298-307     Citation Subset:  IM    
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, Brazil.
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MeSH Terms
Acetophenones / administration & dosage*
Antioxidants / administration & dosage*
Blood Pressure Determination
Cyclic N-Oxides / administration & dosage*
Dicarbethoxydihydrocollidine / analogs & derivatives,  metabolism
Hypertension, Renovascular / enzymology,  pathology,  physiopathology
Matrix Metalloproteinase 2 / genetics,  metabolism*
Organ Culture Techniques
Oxidative Stress / physiology
Rats, Wistar
Reactive Oxygen Species / metabolism
Renal Artery / metabolism*,  pathology,  surgery
Spin Labels
Thiobarbiturates / metabolism
Vasodilation / drug effects,  physiology
Reg. No./Substance:
0/Acetophenones; 0/Antioxidants; 0/Cyclic N-Oxides; 0/Reactive Oxygen Species; 0/Spin Labels; 0/Thiobarbiturates; 0/dihydroethidine; 2226-96-2/tempol; 498-02-2/acetovanillone; 504-17-6/thiobarbituric acid; 632-93-9/Dicarbethoxydihydrocollidine; EC Metalloproteinase 2

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

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