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This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/H2342    most recent 00511.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Ohlmann, P. Articles by Andriantsitohaina, R. Search for Related Content PubMed PubMed Citation Articles by Ohlmann, P. Articles by Andriantsitohaina, R.

Deletion of MLCK210 induces subtle changes in vascular reactivity but does not affect cardiac function

UMR Centre National de la Recherche Scientifique ¹7034 and ³7081, Université Louis Pasteur, Illkirch, France; and ²Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, Illinois

Submitted 7 June 2004 ; accepted in final form 6 July 2005

Myosin light chain kinase (MLCK) plays a key role in the regulation of actomyosin contraction in a large variety of cells. Two isoforms have been described: a short isoform, widely expressed in smooth muscle cells; and a long isoform (MLCK210), mainly localized in the endothelium. This study investigated the consequences on different cardiovascular parameters of MLCK210 gene deletion using MLCK210 knockout mice and of pharmacological inhibition of the kinase using a specific MLCK inhibitor. Deletion of MLCK210 did not affect systolic blood pressure and heart rate or echocardiographic measurements. Electrocardiographic analysis showed neither atrio- nor intraventricular conduction or repolarization defects. Ex vivo responses of aortic rings to vasoconstrictor and vasodilator agonists were not modified in MLCK210 null mice. However, deletion of MLCK210 attenuated shear stress-induced dilation and produced changes in the balance of endothelial-relaxing factors of small mesenteric arteries (SMA). In particular, a reduced flow-mediated NO-dependent dilation was observed. However, it was partially compensated by enhanced indomethacin-sensitive dilation. No significant changes were detected in the endothelium-derived hyperpolarizing component of the vasodilator response. The above effects of MLCK210 gene deletion were confirmed in SMA from wild-type mice by the use of the MLCK enzymatic inhibitor MMZ-10–057. In summary, deletion of MLCK210 was not associated with abnormalities of main in vivo cardiovascular parameters in mice. This study demonstrates a role for MLCK210 in the regulation of flow-dependent dilation in SMA.

myosin light chain kinase 210; knockout mice; echocardiography; endothelium; vascular reactivity; shear stress

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