title: Effects of chronic exposure to cigarette smoke on canonical transient receptor potential expression in rat pulmonary arterial smooth muscle.
abstract: To clarify the possible mechanism of cigarette smoke (CS)-induced pulmonary hypertension and furthermore provide effective targets for prevention and treatment, the effects of chronic CS on rat pulmonary arterial smooth muscle in vivo and nicotine treatment on rat pulmonary arterial smooth muscle cells (PASMCs) in vitro were investigated. In this study, we demonstrated that chronic CS exposure led to rat weight loss, right ventricular hypertrophy, and pulmonary arterial remodeling. A fluorescence microscope was used to measure intracellular calcium concentration ([Ca(2+)]i) in rat distal PASMCs. Results showed that basal [Ca(2+)]i and store-operated calcium entry (SOCE) levels in PASMCs from 3- and 6-mo CS-exposed rats were markedly higher than those in cells from the unexposed control animals (the increases in 6-mo CS group were more significant than that in 3-mo group), accompanied with increased canonical transient receptor potential 1 (TRPC1) and TRPC6 expression at both mRNA and protein levels in isolated distal PA. Simultaneously, in vitro study showed that nicotine treatment (10 nM) significantly increased basal [Ca(2+)]i and SOCE and upregulated TRPC1 and TRPC6 expression in cultured rat distal PASMCs. TRPC siRNA knockdown strategies revealed that the elevations of basal [Ca(2+)]i and SOCE induced by nicotine in PASMCs were TRPC1 and TRPC6 dependent. These results suggested that chronic CS-induced changes in vascular tone and structure in PA and the development of pulmonary hypertension might be largely due to upregulation of TRPC1 and TRPC6 expression in PASMCs, in which nicotine played an important role.
authors: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China;
authors: Jian
authors: J
authors: Wang
authors: Yuqin
authors: Y
authors: Chen
authors: Chunyi
authors: C
authors: Lin
authors: Jing
authors: J
authors: Jia
authors: Lichun
authors: L
authors: Tian
authors: Kai
authors: K
authors: Yang
authors: Lei
authors: L
authors: Zhao
authors: Ning
authors: N
authors: Lai
authors: Qian
authors: Q
authors: Jiang
authors: Yueqian
authors: Y
authors: Sun
authors: Nanshan
authors: N
authors: Zhong
authors: Pixin
authors: P
authors: Ran
authors: Wenju
authors: W
authors: Lu
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D065627:Familial Primary Pulmonary Hypertension; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects*; D050052:TRPC Cation Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D016278:Ventricular Function, Right / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D018722:Nicotinic Agonists; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; C096351:transient receptor potential cation channel, subfamily C, member 1; D009538:Nicotine
keywords: SOCE; TRPC; cigarette smoke; pulmonary hypertension