Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension

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

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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 Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) but Ca2+-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 (MLCKSMKO) 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. MLCKSMKO 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. MLCKSMKO mice may be a useful model of vascular failure and hypotension.

Original languageEnglish (US)
Pages (from-to)H584-H591
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number2
DOIs
StatePublished - Aug 1 2011

Keywords

  • Contraction
  • Knockout
  • Regulatory light chain
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension'. Together they form a unique fingerprint.

  • Cite this

    He, W. Q., Qiao, Y. N., Zhang, C. H., Peng, Y. J., Chen, C., Wang, P., Gao, Y. Q., Chen, C., Chen, X., Tao, T., Su, X. H., Li, C. J., Kamm, K. E., Stull, J. T., & Zhu, M. S. (2011). Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension. American Journal of Physiology - Heart and Circulatory Physiology, 301(2), H584-H591. https://doi.org/10.1152/ajpheart.01212.2010