Key result
Smooth muscle MLCK knockout in mice lowers basal blood pressure and blunts salt-induced hypertension.
Why the study?
Does smooth muscle-specific knockout of MLCK reduce basal blood pressure and salt-induced hypertension in mice?
Does smooth muscle-specific knockout of MLCK reduce basal blood pressure and salt-induced hypertension in mice?
MLCK is necessary for both physiological and pathological blood pressure regulation, suggesting MLCK(SMKO) mice as a model for vascular failure and hypotension.
MLCK knockout lowers basal BP and blunts salt hypertension in mice; leaves open whether MLCK inhibition is a viable antihypertensive target.
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.
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He et al. (2011) studied Hypertension. Smooth muscle-specific knockout of MLCK vs. Wild-type/control mice (implied) was evaluated on Basal blood pressure and contractile response. Smooth muscle-specific knockout of MLCK in mice significantly lowered basal blood pressure, weakened responses to vasopressors, and reduced salt-induced hypertension below normotensive levels.
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