title: Dexamethasone induces rapid promotion of norepinephrine‑mediated vascular             smooth muscle cell contraction.
abstract: The aim of the present study was to identify the rapid effect of dexamethasone (Dex) on norepinephrine (NE)‑mediated contraction of vascular smooth muscle cells (VSMCs) and to establish the underlying mechanism(s). Rat VSMCs were preincubated with lipopolysaccharide to simulate acute septic shock. Myosin light chain (MLC20) phosphorylation of VSMCs was detected by western blot analysis to observe the effects of Dex on NE‑mediated contraction. Activation of the RhoA/ RhoA kinase (ROCK), extracellular signal‑regulated kinase (ERK) and p38 signaling pathways was detected by western blot analysis to explore the mechanism. It was identified that Dex rapidly promoted NE‑induced phosphorylation of MLC20 in VSMCs and this effect may be non‑genomic. The RhoA/ROCK, ERK and p38 pathways were demonstrated to be important for the rapid effect of Dex‑induced promotion of NE‑mediated contraction in VSMCs. The present results indicate that Dex may rapidly reverse the hyporeactivity of vasoconstriction to NE in vitro and this effect may be mediated by specific non‑genomic mechanisms through increased activation of the RhoA/ROCK, ERK and p38 signaling pathways.
authors.affiliation: Department of Nautical Medicine and Laboratory of Stress Medicine,                     Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Wen-Lei
authors.initials: WL
authors.lastname: Shi
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Tasker
authors.forename: Jiang-Rui
authors.initials: JR
authors.lastname: Zhou
authors.forename: Yun-Li
authors.initials: YL
authors.lastname: Peng
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Miao
authors.forename: Yong-Ji
authors.initials: YJ
authors.lastname: Yang
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018994:Myosin Light Chains; D014662:Vasoconstrictor Agents; D003907:Dexamethasone; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D020742:rhoA GTP-Binding Protein; D009638:Norepinephrine