Document Detail

Losartan improves resistance artery lesions and prevents CTGF and TGF-beta production in mild hypertensive patients.
MedLine Citation:
PMID:  16482098     Owner:  NLM     Status:  MEDLINE    
Although structural and functional changes of resistance arteries have been proposed to participate in arterial hypertension (HTA) outcome, not all therapies may correct these alterations, even if they normalize the blood pressure (BP). The aim of this study was to investigate the mechanisms of the protection afforded by the angiotensin receptor antagonist losartan in resistance arteries from patients with essential HTA. In all, 22 untreated hypertensive patients were randomized to receive losartan or amlodipine for 1 year and the morphological characteristics of resistance vessels from subcutaneous biopsies were evaluated. Protein expression of connective tissue growth factor (CTGF), transforming growth factor beta (TGF-beta), and collagens III and IV was detected by immunohistochemistry. In comparison with normotensive subjects, resistance arteries from hypertensive patients showed a significant media:lumen (M/L) ratio increment and a higher protein expression of CTGF, TGF-beta, and collagens. After 1 year of treatment, both losartan and amlodipine similarly controlled BP. However, M/L only decreased in patients under losartan treatment, whereas in the amlodipine-treated group this ratio continued to increase significantly. The administration of losartan prevented significant increments in CTGF, TGF-beta, and collagens in resistance arteries. By contrast, amlodipine-treated patients showed a higher vascular CTGF, TGF-beta, and collagen IV staining than before treatment. Our results show that the administration of losartan, but not amlodipine, to hypertensive patients improves structural abnormalities and prevents the production of CTGF and TGF-beta in small arteries, despite similar BP lowering. These data may explain the molecular mechanisms of the better vascular protection afforded by drugs interfering with the renin-angiotensin system.
D Gómez-Garre; J L Martín-Ventura; R Granados; T Sancho; R Torres; M Ruano; J García-Puig; J Egido
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney international     Volume:  69     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-30     Completed Date:  2006-08-10     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1237-44     Citation Subset:  IM    
Vascular Biology and Atherosclerosis Research Laboratory, Medicina Interna III, Hospital Clínico San Carlos, Madrid, Spain.
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MeSH Terms
Amlodipine / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Antihypertensive Agents / therapeutic use
Arteries / pathology,  physiology,  physiopathology*
Connective Tissue Growth Factor
Hypertension / drug therapy*
Immediate-Early Proteins / physiology*
Intercellular Signaling Peptides and Proteins / physiology*
Losartan / therapeutic use*
Middle Aged
Reference Values
Transforming Growth Factor beta / antagonists & inhibitors*
Vascular Resistance / drug effects*
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/CTGF protein, human; 0/Immediate-Early Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Transforming Growth Factor beta; 114798-26-4/Losartan; 139568-91-5/Connective Tissue Growth Factor; 88150-42-9/Amlodipine
Comment In:
Kidney Int. 2006 Apr;69(7):1104-5   [PMID:  16609677 ]

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

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