Pulmonary hypertension (PH) is a chronic and complex condition characterized by structural alterations in the pulmonary vasculature, leading to vascular remodeling, increased pulmonary vascular resistance, and heightened vasoreactivity. Although nicotine exposure is demonstrated to adversely affect the structure and function of pulmonary arteries, the underlying molecular mechanisms remain incompletely elucidated. After eight weeks of nicotine exposure, right ventricular systolic pressure (RVSP) increased in a concentration-dependent manner with nicotine doses, accompanied by a progressive reduction in tricuspid annular plane systolic excursion (TAPSE). Nicotine-treated mice exhibited a significant increase in respiratory frequency, whereas expiratory flow at 50%, peak inspiratory flow, peak expiratory flow, and tidal volume showed concentration-dependent decreases. Furthermore, pulmonary arteries from nicotine-exposed mice displayed enhanced concentrationdependent contractions in response to vasoconstrictor. Notably, partial smooth-muscle Cx43 deficiency not only depressed the changes of RVSP, TAPSE and the pulmonary function parameters but also reduced pulmonary artery hyperreactivity. Additionally, nicotine treatment significantly inhibited the contractile response of pulmonary arteries to (4-AP), which was associated with decreased protein levels of Kv1.2 and Kv2.1. Importantly, partial smooth-muscle Cx43 deficiency reversed the nicotine-induced changes in pulmonary arterial hyperreactivity, Kv1.2 and Kv2.1 expression. Collectively, Cx43 upregulation, with subsequent downregulation of Kv1.2 and Kv2.1, drives nicotine-induced pulmonary arterial dysfunction.
[1]Shanxi Med Univ, Dept Pharmacol, 56 Xinjian South Rd, Taiyuan 030001, Shanxi, Peoples R China.
[2]Shanxi Med Univ, Environm Exposures Vasc Dis Inst, 56 Xinjian South Rd, Taiyuan 030001, Shanxi, Peoples R China.
[3]Shanxi Med Univ, China Key Lab Cellular Physiol, Taiyuan 030001, Shanxi, Peoples R China.
[4]Shanxi Med Univ, Acad Med Sci, 56 Xinjian South Rd, Taiyuan 030001, Shanxi, Peoples R China.
[5]Shanxi Med Univ, Sch Publ Hlth, 56 Xinjian South Rd, Taiyuan 030001, Shanxi, Peoples R China.
[6]Chinese Acad Med Sci, China Japan Friendship Hosp,State Key Lab Resp Hlt, Ctr Resp Med,Dept Pulm & Crit Care Med, Inst Resp Med,Natl Ctr Resp Med,Natl Clin Res Ctr, Beijing, Peoples R China.
[7]Shanxi Med Univ, Dept Phys Educ, 56 Xinjian South Rd, Taiyuan 030001, Shanxi, Peoples R China.
[8]Shanxi Coal Cent Hosp, Pediat, 101 Xuefu St, Taiyuan 0300061, Shanxi, Peoples R China.
[9]Shanxi Med Univ, Hosp 1, Taiyuan 030001, Shanxi, Peoples R China.
[10]Minist Educ, Key Lab Coal Environm Pathogen & Prevent, Taiyuan 030001, Shanxi, Peoples R China.
[11]Shanxi Med Univ, Hosp 1, Dept Pulm & Crit Care Med, NHC Key Lab Pneumoconiosis, Taiyuan 030001, Shanxi, Peoples R China.
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