Document Detail


Hypertension impairs postnatal vasculogenesis: role of antihypertensive agents.
MedLine Citation:
PMID:  18426993     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We analyzed the effect of hypertension on postischemic vasculogenesis. Ischemia was induced by right femoral artery ligature in Wistar Kyoto rats (WKY) or spontaneously hypertensive rats (SHR) treated with or without angiotensin-converting enzyme inhibitor (Perindopril, 0.76 mg/kg/d) and angiotensin type 1 receptor blocker (losartan, 30 mg/kg/d). Basal postischemic neovascularization was reduced in SHR compared to WKY (P<0.05, n=8). Treatment with ACE inhibitor or angiotensin type 1 receptor blocker decreased blood pressure levels by 1.4- and 1.3-fold (P<0.001), respectively and restored vessel growth in SHR to WKY levels. Interestingly, 14 days after bone-marrow mononuclear cell (BM-MNC) transfusion, angiographic scores, capillary density, and foot perfusion were decreased by 1.4-, 1.5-, and 1.2-fold, respectively in SHR transfused with BM-MNCs isolated from SHR compared to those receiving BM-MNCs of WKY (P<0.05, n=6). Alteration in BM-MNCs proangiogenic potential was likely related to the reduction in their ability to mobilize into peripheral circulation, as revealed by the 2.9-fold decrease in number of circulating CD34+/CD117+ cells (P<0.001) and to differentiate into cells with endothelial phenotype, as revealed by the 2.1-fold reduction in percentages of DilLDL/BS-1 lectin positive cells (P<0.001). In addition, reactive oxygen species (ROS) levels were increased by 2.2-fold in SHR BM-MNCs compared to WKY BM-MNCs (P<0.01), as assessed by L-012 luminescence. Cotreatment with ACE inhibitor, angiotensin type 1 receptor blocker, or antioxidants (NAC 3 mmol/L, Apocynin 200 micromol/L) reduced ROS levels, improved the number of DilLDL/BS-1 lectin-positive cells by around 1.5-fold, and restored BM-MNCs proangiogenic effects in ischemic hindlimb. In conclusion, alteration in progenitor cell proangiogenic function may participate to the hypertension-induced impairment in postischemic revascularization.
Authors:
Dong You; Clément Cochain; Céline Loinard; José Vilar; Barend Mees; Micheline Duriez; Bernard I Lévy; Jean-Sébastien Silvestre
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-21
Journal Detail:
Title:  Hypertension     Volume:  51     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-23     Completed Date:  2008-06-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1537-44     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Center INSERM U689 Lariboisière, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / pharmacology*
Blood Pressure / drug effects,  physiology
Bone Marrow Cells / cytology,  physiology
Cell Differentiation / physiology
Disease Models, Animal
Endothelium, Vascular / cytology,  physiology
Hindlimb / blood supply
Hydralazine / pharmacology
Hypertension / drug therapy*,  pathology,  physiopathology*
Ischemia / pathology,  physiopathology
Ligation
Losartan / pharmacology
Male
Neovascularization, Physiologic / drug effects*,  physiology*
Oxidative Stress / drug effects,  physiology
Perindopril / pharmacology*
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Stem Cells / cytology,  physiology
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 114798-26-4/Losartan; 82834-16-0/Perindopril; 86-54-4/Hydralazine

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


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