Document Detail

Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension.
MedLine Citation:
PMID:  21572007     Owner:  NLM     Status:  MEDLINE    
Vascular tone, an important determinant of systemic vascular resistance and thus blood pressure, is affected by vascular smooth muscle (VSM) contraction. Key signaling pathways for VSM contraction converge on phosphorylation of the regulatory light chain (RLC) of smooth muscle myosin. This phosphorylation is mediated by Ca(2+)/calmodulin-dependent myosin light chain kinase (MLCK) but Ca(2+)-independent kinases may also contribute, particularly in sustained contractions. Signaling through MLCK has been indirectly implicated in maintenance of basal blood pressure, whereas signaling through RhoA has been implicated in salt-induced hypertension. In this report, we analyzed mice with smooth muscle-specific knockout of MLCK. Mesenteric artery segments isolated from smooth muscle-specific MLCK knockout mice (MLCK(SMKO)) had a significantly reduced contractile response to KCl and vasoconstrictors. The kinase knockout also markedly reduced RLC phosphorylation and developed force. We suggest that MLCK and its phosphorylation of RLC are required for tonic VSM contraction. MLCK(SMKO) mice exhibit significantly lower basal blood pressure and weaker responses to vasopressors. The elevated blood pressure in salt-induced hypertension is reduced below normotensive levels after MLCK attenuation. These results suggest that MLCK is necessary for both physiological and pathological blood pressure. MLCK(SMKO) mice may be a useful model of vascular failure and hypotension.
Wei-Qi He; Yan-Ning Qiao; Cheng-Hai Zhang; Ya-Jing Peng; Chen Chen; Pei Wang; Yun-Qian Gao; Caiping Chen; Xin Chen; Tao Tao; Xiao-Hong Su; Chao-Jun Li; Kristine E Kamm; James T Stull; Min-Sheng Zhu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-13
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-02     Completed Date:  2011-09-30     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H584-91     Citation Subset:  IM    
Model Animal Research Center and MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China.
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MeSH Terms
Blood Pressure* / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Hypertension / enzymology*,  etiology,  physiopathology
Mesenteric Arteries / enzymology,  physiopathology
Mice, Knockout
Muscle, Smooth, Vascular / drug effects,  enzymology*,  physiopathology
Myosin Light Chains / metabolism
Myosin-Light-Chain Kinase / deficiency,  genetics,  metabolism*
Potassium Chloride / pharmacology
Sodium Chloride, Dietary*
Time Factors
Vasoconstriction* / drug effects
Vasoconstrictor Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Myosin Light Chains; 0/Sodium Chloride, Dietary; 0/Vasoconstrictor Agents; 64-85-7/Desoxycorticosterone; 7447-40-7/Potassium Chloride; EC Kinase

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