Norepinephrine reversibly regulates the proliferation and phenotypic transformation of vascular smooth muscle cells

objective: To investigate the effect of norepinephrine (NE) on the proliferation and phenotypic transformation of vascular smooth muscle cells (VSMCs) and the mechanisms underlying this effect. Methods: VSMCs were isolated from the rat abdominal aorta. VSMCs cultured in both serum-containing or in a serum-free medium were treated with NE, oxidized low-density lipoprotein (ox-LDL), alpha-adrenergic receptor agonist (alpha 1-R-), beta 1-adrenergic receptor antagonist (beta 1-R-) and various combinations of these factors. VSMC proliferation was determined by bromodeoxyuridine (BrdU) assays. The mRNA expression level of HRG-1 and SM22 alpha were determined by reverse transcription-polymerase chain reaction (RT-PCR). Results: The expressions of HRG-1 and SM22 alpha mRNA in NE- or OX-LDL-treated VSMCs was down-regulated, and the proliferation of BrdU-labeled cells increased; the expression of the abovementioned genes in the VSMCs treated with a combination of NE, alpha 1-R, and beta 1-R was significantly up-regulated. However, NE was observed to up-regulate the expression of HRG-1 and SM22 alpha mRNA in serum-starved VSMCs. Conclusion: NE could reversibly regulate the proliferation and phenotypic transformation of VSMCs. This regulation might be mediated via its receptors. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.