首页> 外文期刊>American Journal of Physiology >Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension.
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Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension.

机译:肌球蛋白轻链激酶在基础血压调节中的作用及盐诱导高血压的维持。

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摘要

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.
机译:血管间调,全身血管抗性和血压的重要决定因素受血管平滑肌(VSM)收缩的影响。用于VSM收缩的关键信号通路与平滑肌肌球蛋白的调节轻链(RLC)的磷酸化收敛。该磷酸化由Ca(2 +)/钙调蛋白依赖性肌蛋白轻链激酶(MLCK)介导,但Ca(2 +) - 依赖性激酶也可以有助于持续收缩。通过MLCK的信号通知已经间接地涉及维持基础血压,而通过RHOA的信号传导涉及盐诱导的高血压。在本报告中,我们分析了MLCK的平滑肌敲除的小鼠。从平滑肌特异性的微克敲除小鼠(MLCK(SMKO))分离的肠系膜动脉段具有显着降低的KCl和血管科技的收缩响应。激酶敲除还显着降低了RLC磷酸化和发育力。我们建议滋补VSM收缩需要MLCK及其对RLC的磷酸化。 MLCK(SMKO)小鼠表现出显着降低的基础血压和对血管加压器的反应较弱。在MLCK衰减后,盐诱导的高血压的血压升高降低了正常的水平。这些结果表明MLCK对于生理和病理血压都是必要的。 MLCK(SMKO)小鼠可以是血管衰竭和低血压的有用模型。

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