Myosin light chain kinase is necessary for post-shock
mesenteric lymph drainage enhancement of vascular reactivity and calcium
sensitivity in hemorrhagic-shocked rats |
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Authors: | Y.P. Zhang C.Y. Niu Z.G. Zhao L.M. Zhang Y.H. Si |
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Affiliation: | Institute of Microcirculation, Hebei North University, Hebei, China |
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Abstract: | Vascular hyporeactivity is an important factor in irreversible shock, andpost-shock mesenteric lymph (PSML) blockade improves vascular reactivity afterhemorrhagic shock. This study explored the possible involvement of myosin lightchain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calciumdesensitization. Rats were divided into sham (n=12), shock (n=18), andshock+drainage (n=18) groups. A hemorrhagic shock model (40±2 mmHg, 3 h) wasestablished in the shock and shock+drainage groups. PSML drainage was performedfrom 1 to 3 h from start of hypotension in shock+drainage rats. Levels ofphospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA)tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity toCa2+ were observed in SMA rings in an isolated organ perfusionsystem. p-MLCK was significantly decreased in the shock group compared with thesham group, but increased in the shock+drainage group compared with the shockgroup. Substance P (1 nM), an agonist of MLCK, significantly elevated thedecreased contractile response of SMA rings to both NE and Ca2+ atvarious concentrations. Maximum contractility (Emax) in the shockgroup increased with NE (from 0.179±0.038 to 0.440±0.177 g/mg, P<0.05) andCa2+ (from 0.515±0.043 to 0.646±0.096 g/mg, P<0.05). ML-7 (0.1nM), an inhibitor of MLCK, reduced the increased vascular response to NE andCa2+ at various concentrations in the shock+drainage group (from0.744±0.187 to 0.570±0.143 g/mg in Emax for NE and from 0.729±0.037to 0.645±0.056 g/mg in Emax for Ca2+, P<0.05). Weconclude that MLCK is an important contributor to PSML drainage, enhancingvascular reactivity and calcium sensitivity in rats with hemorrhagic shock. |
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Keywords: | Hemorrhagic shock Mesenteric lymph Drainage Myosin light chain kinase (MLCK) Vascular reactivity Calcium sensitivity |
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