title: Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats.
abstract: Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40 ± 2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca²⁺ were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca²⁺ at various concentrations. Maximum contractility (Emax) in the shock group increased with NE (from 0.179 ± 0.038 to 0.440 ± 0.177 g/mg, P<0.05) and Ca²⁺ (from 0.515 ± 0.043 to 0.646 ± 0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca²⁺ at various concentrations in the shock+drainage group (from 0.744 ± 0.187 to 0.570 ± 0.143 g/mg in Emax for NE and from 0.729 ± 0.037 to 0.645 ± 0.056 g/mg in Emax for Ca²⁺, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.
authors.affiliation: Institute of Microcirculation, Hebei North University, Hebei, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Zhang
authors.forename: C Y
authors.initials: CY
authors.lastname: Niu
authors.forename: Z G
authors.initials: ZG
authors.lastname: Zhao
authors.forename: L M
authors.initials: LM
authors.lastname: Zhang
authors.forename: Y H
authors.initials: YH
authors.lastname: Si
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008196:Lymph / Q000502:physiology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000503:physiopathology*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000032:analysis / Q000502:physiology*; D011897:Random Allocation; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000201:enzymology / Q000503:physiopathology*
chemical_list: D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase; D002118:Calcium
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