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. Copyright © 2013 Spandidos Publications Ltd.