Xiaomin Hou, Xuelu Jiang, Xin Meng, Jin Zhou, Di Xi, Xiaoxia Ren, Ming Gao, Yong’e Liu, Xiao Luo Yiwei Shi, Xiaojiang Qin
Shanxi Medical University. China-Japan Friendship Hospital. Shanxi Coal Central Hospital. First hospital of Shanxi Medical University.
China
Food and Chemical Toxicology
Food Chem Toxicol 2026;
DOI: 10.1016/j.fct.2026.116182
Abstract
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 concentration-dependent 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.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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