Document Detail

Intravascular pressure augments cerebral arterial constriction by inducing voltage-insensitive Ca2+ waves.
MedLine Citation:
PMID:  20736418     Owner:  NLM     Status:  MEDLINE    
This study examined whether elevated intravascular pressure stimulates asynchronous Ca(2+) waves in cerebral arterial smooth muscle cells and if their generation contributes to myogenic tone development. The endothelium was removed from rat cerebral arteries, which were then mounted in an arteriograph, pressurized (20-100 mmHg) and examined under a variety of experimental conditions. Diameter and membrane potential (V(M)) were monitored using conventional techniques; Ca(2+) wave generation and myosin light chain (MLC(20))/MYPT1 (myosin phosphatase targeting subunit) phosphorylation were assessed by confocal microscopy and Western blot analysis, respectively. Elevating intravascular pressure increased the proportion of smooth muscle cells firing asynchronous Ca(2+) waves as well as event frequency. Ca(2+) wave augmentation occurred primarily at lower intravascular pressures (<60 mmHg) and ryanodine, a plant alkaloid that depletes the sarcoplasmic reticulum (SR) of Ca(2+), eliminated these events. Ca(2+) wave generation was voltage insensitive as Ca(2+) channel blockade and perturbations in extracellular [K(+)] had little effect on measured parameters. Ryanodine-induced inhibition of Ca(2+) waves attenuated myogenic tone and MLC(20) phosphorylation without altering arterial V(M). Thapsigargin, an SR Ca(2+)-ATPase inhibitor also attenuated Ca(2+) waves, pressure-induced constriction and MLC(20) phosphorylation. The SR-driven component of the myogenic response was proportionally greater at lower intravascular pressures and subsequent MYPT1 phosphorylation measures revealed that SR Ca(2+) waves facilitated pressure-induced MLC(20) phosphorylation through mechanisms that include myosin light chain phosphatase inhibition. Cumulatively, our findings show that mechanical stimuli augment Ca(2+) wave generation in arterial smooth muscle and that these transient events facilitate tone development particularly at lower intravascular pressures by providing a proportion of the Ca(2+) required to directly control MLC(20) phosphorylation.
Rania E Mufti; Suzanne E Brett; Cam Ha T Tran; Rasha Abd El-Rahman; Yana Anfinogenova; Ahmed El-Yazbi; William C Cole; Peter P Jones; S R Wayne Chen; Donald G Welsh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-24
Journal Detail:
Title:  The Journal of physiology     Volume:  588     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-01-28     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  3983-4005     Citation Subset:  IM    
Hotchkiss Brain Institute, Libin Cardiovascular Institute, Department of Physiology & Pharmacology, University of Calgary, Alberta, Canada.
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MeSH Terms
Blotting, Western
Calcium Signaling / drug effects,  physiology*
Cerebral Arteries / drug effects,  physiology*
Endothelium, Vascular / drug effects,  physiology*
Enzyme Inhibitors / pharmacology
Membrane Potentials / drug effects,  physiology
Microscopy, Confocal
Muscle, Smooth, Vascular / drug effects,  physiology*
Myocytes, Smooth Muscle / drug effects,  physiology*
Phosphorylation / drug effects,  physiology
Rats, Sprague-Dawley
Ryanodine / pharmacology
Sarcoplasmic Reticulum / drug effects,  metabolism
Thapsigargin / pharmacology
Vasoconstriction / drug effects,  physiology*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Enzyme Inhibitors; 15662-33-6/Ryanodine; 67526-95-8/Thapsigargin

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

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