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: Y P Zhang, C Y Niu, Z G Zhao, L M Zhang, Y H Si
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 46 Issue 7 Pg. 574-9 (Jul 2013) ISSN: 1414-431X [Electronic] Brazil
• PMID: 23903684 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Myosin Light Chains
• Myosin-Light-Chain Kinase
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Lymph (physiology)
• Male
• Mesenteric Artery, Superior (metabolism, physiopathology)
• Muscle Contraction
• Muscle, Smooth, Vascular (metabolism, physiopathology)
• Myosin Light Chains (metabolism)
• Myosin-Light-Chain Kinase (analysis, physiology)
• Random Allocation
• Rats, Wistar
• Shock, Hemorrhagic (enzymology, physiopathology)