Document Detail


Temporal alterations in basement membrane components in the pulmonary vasculature of the chronically hypoxic rat: impact of hypoxia and recovery.
MedLine Citation:
PMID:  8701968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The hypoxic model of pulmonary hypertension was used to examine temporal alterations in the deposition of the basement membrane (BM) and components of fibronectin, laminin, and Type IV collagen within vascular, airway, and gas exchange compartments of the lung. Because hypoxic pulmonary hypertension is a reversible model of hypertension, changes in fibronectin and laminin synthesis/deposition in the recovering lung were also examined. Long-term hypoxic exposure produced decreases in body weight, increased right ventricular and lung dry weights and elevations in pulmonary arterial pressure. Immunohistochemical analysis revealed consistent and progressive increases in the deposition of fibronectin and laminin, but not type IV collagen, in the subendothelial and medial BMs of large and small pulmonary arteries, but not in airways or lung parenchyma. These changes were observed by day 4 of hypoxia and were most prominent in the conducting vasculature. Northern analysis showed a biphasic pattern of alterations in steady-state levels of BM component mRNA in hypoxic rats with early reductions at days 4 and 7 followed by increases at day 12. Recovery from 12 days of hypoxia resulted in regression of pulmonary hypertension and right ventricular hypertrophy but not increased lung weight. Immunohistochemical analysis of fibronectin, laminin, and type IV collagen levels in the vasculature showed a temporal regression to levels that were not remarkably different from time-matched controls at day 30 of recovery. Northern analysis of lungs from hypoxic-recovery rats revealed increased steady-state levels of mRNA for fibronectin, laminin, and type IV collagen at all time points. These data indicate that long-term hypoxic exposure elicits marked alterations in the synthetic capacity and deposition of the important cell attachment BM glycoproteins fibronectin and laminin. In addition, recovery from hypoxia appears to be characterized by a lack of increased fibronectin and laminin levels in the conducting vasculature, suggesting a marked and rapid reorganization of the vascular BMs on both hypoxic exposure and recovery from hypoxia.
Authors:
A C Vyas-Somani; S M Aziz; S A Arcot; M N Gillespie; J W Olson; D W Lipke
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of the medical sciences     Volume:  312     ISSN:  0002-9629     ISO Abbreviation:  Am. J. Med. Sci.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-09-05     Completed Date:  1996-09-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370506     Medline TA:  Am J Med Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  54-67     Citation Subset:  AIM; IM    
Affiliation:
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, Chandler Medical Center, University of Kentucky, Lexington 40536-0082, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / metabolism*,  pathology
Basement Membrane / metabolism*,  pathology
Blotting, Northern
Collagen / metabolism
Disease Models, Animal
Fibronectins / metabolism
Histocytochemistry
Hypertension, Pulmonary / metabolism*,  pathology
Laminin / metabolism
Lung / blood supply,  metabolism*,  pathology
Male
Pulmonary Artery / metabolism,  pathology
RNA, Messenger / analysis
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
HL02174/HL/NHLBI NIH HHS; HL36404/HL/NHLBI NIH HHS; HL43831/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Laminin; 0/RNA, Messenger; 9007-34-5/Collagen

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


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