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J Vasc Res. 2011;48(2):150-62. doi: 10.1159/000318804. Epub 2010 Oct 8.

Marfan syndrome decreases Ca2+ wave frequency and vasoconstriction in murine mesenteric resistance arteries without changing underlying mechanisms.

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  • 1Department of Anesthesiology, Pharmacology and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, B.C., Canada.

Abstract

BACKGROUND/AIMS:

Vascular smooth muscle in Marfan syndrome, a connective tissue disorder caused by mutations in FBN1 encoding fibrillin-1, is associated with decreased tonic contraction. As Ca(2+) waves are tightly associated with vasoconstriction, we hypothesized decreased tonic contraction in Marfan syndrome is due to aberrant Ca(2+) wave signaling.

METHODS:

Isometric force and intracellular Ca(2+) were measured from second-order mesenteric arteries from mice heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1(C1039G/+)).

RESULTS:

Phenylephrine concentration-dependently induced tonic contraction associated with sustained repetitive oscillations in intracellular [Ca(2+)] in both control and Marfan vessels, although Marfan vessels displayed significantly decreased Ca(2+) wave frequency and decreased number of cells exhibiting waves. Inhibition of sarcoplasmic reticulum Ca(2+) re-uptake by cyclopiazonic acid abolished Ca(2+) waves, dramatically decreasing tonic contraction. Nifedipine significantly reduced Ca(2+) wave frequency and tonic contraction, while the nifedipine-insensitive component was abolished by SKF-96365. Ca(2+) waves and tonic contraction were abolished by 2-aminoethoxydiphenylborate, but were unaffected by ryanodine or tetracaine.

CONCLUSION:

Phenylephrine-induced Ca(2+) waves underlie tonic contraction in resistance-sized mesenteric arteries and appear to be produced by repetitive cycles of regenerative Ca(2+) release from the sarcoplasmic reticulum. Decreased frequency of Ca(2+) waves in Marfan syndrome appears to be responsible for reduced tonic contraction.

Copyright © 2010 S. Karger AG, Basel.

PMID:
20926894
[PubMed - indexed for MEDLINE]
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