Document Detail


Dysfunction of endothelial and smooth muscle cells in small arteries of a mouse model of Marfan syndrome.
MedLine Citation:
PMID:  19814726     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Marfan syndrome, a connective tissue disorder caused by mutations in FBN1 encoding fibrillin-1, results in life-threatening complications in the aorta, but little is known about its effects in resistance vasculature.
EXPERIMENTAL APPROACH: Second-order mesenteric arteries from mice at 3, 6 and 10 months of age (n= 30) heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1(C1039G/+)) were compared with those from age-matched control littermates.
KEY RESULTS: Stress-strain curves indicated that arterial stiffness was increased at 6 and 10 months of age in Marfan vessels. Isometric force measurement revealed that contraction in response to potassium (60 mM)-induced membrane depolarization was decreased by at least 28% in Marfan vessels at all ages, while phenylephrine (3 microM)-induced contraction was reduced by at least 40% from 6 months. Acetylcholine-induced relaxation in Marfan vessels was reduced to 70% and 45% of control values, respectively, at 6 and 10 months. Sensitivity to sodium nitroprusside was reduced at 6 months (pEC(50)= 5.64 +/- 0.11, control pEC(50)= 7.34 +/- 0.04) and 10 months (pEC(50)= 5.99 +/- 0.07, control pEC(50)= 6.99 +/- 0.14). Pretreatment with N(omega)-Nitro-L-arginine methyl ester (200 microM) had no effect on acetylcholine-induced relaxation in Marfan vessels, but reduced vasorelaxation in control vessels to 57% of control values. Addition of indomethacin (10 microM) and catalase (1000 U.mL(-1)) further inhibited vasorelaxation in Marfan vessels to a greater degree compared with control vessels.
CONCLUSIONS AND IMPLICATIONS: Pathogenesis of Marfan syndrome in resistance-sized arteries increases stiffness and impairs vasomotor function.
Authors:
H T Syyong; A W Y Chung; H H C Yang; C van Breemen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-08
Journal Detail:
Title:  British journal of pharmacology     Volume:  158     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-12     Completed Date:  2010-02-25     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1597-608     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Age Factors
Alleles
Animals
Disease Models, Animal
Elasticity
Endothelium, Vascular / drug effects,  pathology*
Marfan Syndrome / genetics,  physiopathology*
Mesenteric Arteries / cytology,  drug effects,  pathology
Mice
Mice, Inbred C57BL
Microfilament Proteins / genetics*
Myocytes, Smooth Muscle / drug effects,  pathology*
Nitroprusside / pharmacology
Phenylephrine / pharmacology
Vasoconstriction / drug effects
Vasoconstrictor Agents / pharmacology
Vasodilation / drug effects
Vasodilator Agents / pharmacology
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Microfilament Proteins; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 0/fibrillin; 15078-28-1/Nitroprusside; 51-84-3/Acetylcholine; 59-42-7/Phenylephrine
Comments/Corrections

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


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