Effect of KV and KATP channels in nicotine-induced enhancement of pulmonary artery tone in mice
Objective To investigate the role of four potassium ion channels in nicotine-induced augmentation of pulmonary artery tone in mice.Methods Forty C57BL/6J mice were randomly divided into four groups,control group(free water and food intake),nicotine low-dose group(0.02 mg/kg d nose-drop),nicotine medium-dose group(0.2 mg/kg d nose-drop),and nicotine high-dose group(2 mg/kg·d nose-drop)were infected with the drug for 8 weeks.Morphological changes of pulmonary arteries in each group were detected by HE staining.Pulmonary arteries of mice were acutely isolated,and the internal diameters of the tertiary branches of pulmonary arteries in each group were determined by using a wire myograph(DMT)and software.The constrictive effect of nicotine(10-11～10-5 mol/L)on pulmonary arteries of C57BL/6J mice was examined by using a wire myograph and vascular constrictors(KCl,PE,NE,and AngⅡ)on small pulmonary arteries in each group of mice.Four potassium channel inhibitors(KV channel inhibitor 4-AP,KCa channel inhibitor TEA,KATP channel inhibitor Gli,and Kir channel inhibitor BaCl2)were preincubated to detect their effects on the contraction of small pulmonary arteries by nicotine.Results(1)HE staining result showed that the wall of mouse pulmonary arteries was thickened,the lumen was narrowed,and perivascular inflammatory tissue infiltration was obvious after nicotine intervention,and the degree of remodeling of pulmonary arteries increased with increasing concentrations of nicotine intervention;(2)The internal diameter of small pulmonary arteries in mice decreased gradually with increasing concentrations of nicotine droplets.(3)The result of the DMT ex vivo vascular tone assay showed that in vitro incubation with nicotine(10-11～10-5 mol/L),could concentration-dependently induce contraction of small pulmonary arteries in mice.(4)All four vasoconstrictors(KCl,PE,NE,and AngⅡ)produced a contractile effect on pulmonary arteries in mice;and the degree of contraction of pulmonary arteries was gradually enhanced with the increase of the concentration of nicotine drop-nose intervention.(5)After preincubation with 10-8 mol/L 4-AP and 10-6 mol/L Gli,the contraction of pulmonary arteries by nicotine was significantly enhanced(F4-AP=90.851,FGli=16.490,P＜0.001),whereas the enhancement of contraction of pulmonary arteries by nicotine after preincubation with 10-8 mol/L TEA and 10-7 mol/L BaCl2 was not statistically significant.Conclusion Nicotine exposure could cause increased pulmonary artery tone in C57BL/6J mice which maybe associated with the synergistic effects of KV and KATP.
万方数据
维普
