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

40 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number2
DOIs
StatePublished - Aug 2011

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Myosin-Light-Chain Kinase
Salts
Maintenance
Blood Pressure
Hypertension
Muscle Contraction
Vascular Smooth Muscle
Phosphorylation
Smooth Muscle Myosins
Light
Phosphotransferases
Mesenteric Arteries
Vasoconstrictor Agents
Calmodulin
Knockout Mice
Vascular Resistance
Hypotension
Smooth Muscle
Blood Vessels

Keywords

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

ASJC Scopus subject areas

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

Cite this

Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension. / He, Wei Qi; Qiao, Yan Ning; Zhang, Cheng Hai; Peng, Ya Jing; Chen, Chen; Wang, Pei; Gao, Yun Qian; Chen, Caiping; Chen, Xin; Tao, Tao; Su, Xiao Hong; Li, Chao Jun; Kamm, Kristine E.; Stull, James T.; Zhu, Min Sheng.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 301, No. 2, 08.2011.

Research output: Contribution to journalArticle

He, Wei Qi ; Qiao, Yan Ning ; Zhang, Cheng Hai ; Peng, Ya Jing ; Chen, Chen ; Wang, Pei ; Gao, Yun Qian ; Chen, Caiping ; Chen, Xin ; Tao, Tao ; Su, Xiao Hong ; Li, Chao Jun ; Kamm, Kristine E. ; Stull, James T. ; Zhu, Min Sheng. / Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension. In: American Journal of Physiology - Heart and Circulatory Physiology. 2011 ; Vol. 301, No. 2.
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