title: DMSO-soluble cigarette smoke particles alter the expression of endothelin B receptor in rat coronary artery.
abstract: In coronary artery diseases, cigarette smoking is a risk factor and the endothelin system plays a key role in the pathogenesis. This study was to examine if dimethylsulfoxide-soluble smoke particles (DSP) upregulate endothelin type-B (ETB) receptors in the coronary artery and investigate the mechanism. The isolated rat coronary arteries were organ-cultured for 24 h. The contractile response of the coronary artery was recorded by myograph. The mRNA and protein expression of the ETB receptors was studied using quantitative real-time PCR and immunohistochemistry. Results showed that the ETB receptor agonist, sarafotoxin 6c, induced a weak contraction in the fresh coronary artery. After culture, the contraction curve mediated by ETB receptor was shifted towards the left with an increased Emax of 152 ± 12%. DSP of 0.2 and 0.4 μl/ml shifted the concentration-contractile curves towards the left with further increased Emax of 270 ± 26 and 280 ± 29%, respectively. The culture increased ETB receptor mRNA and protein levels from fresh arteries, which was further enhanced by DSP. PD98059 (ERK1/2 inhibitor), wedelolactone (NF-κB inhibitor), actinomycin D or cycloheximide significantly inhibited the DSP-enhanced contraction and expression of mRNA and protein of the ETB receptor. However, SB203580 (p38 inhibitor) further increased DSP-enhanced contraction and protein expression of the ETB receptor. The results indicate that DSP upregulates ETB receptors in rat coronary artery via ERK1/2 and the NF-κB pathway.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, Xi'an, PR China.
authors.forename: Lin-Hong
authors.initials: LH
authors.lastname: Huang
authors.forename: Ping-An
authors.initials: PA
authors.lastname: Zhang
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000737:chemistry / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D009924:Organ Culture Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000032:analysis / Q000187:drug effects / Q000235:genetics*; D012906:Smoke / Q000009:adverse effects / Q000032:analysis*; D012995:Solubility; D014026:Nicotiana; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D012906:Smoke; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D003609:Dactinomycin; D003513:Cycloheximide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004121:Dimethyl Sulfoxide