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Down‐Regulation of α 1 ‐Adrenoceptor Expression by Lipid‐Soluble Smoke Particles through Transcriptional Factor Nuclear Factor‐κB Pathway
Author(s) -
Zhang Wei,
Cao YongXiao,
He JianYu,
Xu CangBao
Publication year - 2007
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2007.00163.x
Subject(s) - cycloheximide , medicine , endocrinology , myograph , vascular smooth muscle , messenger rna , transcription factor , gene expression , receptor , biology , chemistry , contraction (grammar) , microbiology and biotechnology , protein biosynthesis , biochemistry , gene , smooth muscle
Smoking is a strong risk factor for cardiovascular disease that is a leading cause of death and disability in Western countries. The present study was designed to investigate the effect of lipid‐soluble smoke particles (DSP) on α‐adrenoceptor expression in organ culture of rat mesenteric arteries and human epiploon arteries. Myograph and real‐time reverse transcription‐polymerase chain reaction were employed to assess vascular smooth muscle contractibility and the receptor mRNA expression in the smooth muscle cells. Organ culture of the arterial segments in the presence of DSP (0.2 µl/ml) resulted in a significantly decreased contractile response to norepinephrine, compared to control (i.e. in the presence of dimethyl sulfoxide) (P < 0.05). This was in parallel with a down‐regulation of α 1A ‐adrenoceptor mRNA expression in the smooth muscle, while α 2 ‐adrenoceptor mRNA expression remained unchanged. General transcription inhibitor actinomycin D (10 −5.4 M), but not the translational inhibitor cycloheximide (10 −5 M), significantly abolished the DSP‐induced depressed contraction to norepinephrine. IMD‐0354 (10 −7.5 M), a specific nuclear factor‐κB (NF‐κB) pathway inhibitor, markedly reversed the DSP‐induced down‐regulation of α 1A ‐adrenoceptor expression in the smooth muscle at both functional and mRNA levels. Thus, we have demonstrated that smoking‐induced down‐regulation of α 1A ‐adrenoceptor expression was via the transcriptional factor NF‐κB pathway.