| Dysfunction of endothelial and smooth muscle cells in small arteries of a mouse model of Marfan syndrome. | |
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MedLine Citation:
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PMID: 19814726 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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H T Syyong; A W Y Chung; H H C Yang; C van Breemen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-08 |
Journal Detail:
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Title: British journal of pharmacology Volume: 158 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-11-12 Completed Date: 2010-02-25 Revised Date: 2010-11-02 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1597-608 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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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:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Microfilament Proteins; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 0/fibrillin; 15078-28-1/Nitroprusside; 51-84-3/Acetylcholine; 59-42-7/Phenylephrine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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