Impairment of Endothelial Function by Cigarette Smoke Is Not Caused by a Specific Smoke Constituent, but by Vagal Input From the Airway. Issue 11 (27th October 2022)

• Record Type: Journal Article
• Authors: Nabavizadeh, Pooneh; Liu, Jiangtao; Rao, Poonam; Ibrahim, Sharina; Han, Daniel D.; Derakhshandeh, Ronak; Qiu, Huiliang; Wang, Xiaoyin; Glantz, Stanton A.; Schick, Suzaynn F.; Springer, Matthew L.
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 42:Issue 11(2022)
• Page Start: 1324
• Page End: 1332
• Publication Date: 2022-10-27
• Subjects: acetaldehyde -- acrolein -- carbon -- menthol -- nanoparticles; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.122.318051
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Background: Exposure to tobacco or marijuana smoke, or e-cigarette aerosols, causes vascular endothelial dysfunction in humans and rats. We aimed to determine what constituent, or class of constituents, of smoke is responsible for endothelial functional impairment. Methods: We investigated several smoke constituents that we hypothesized to mediate this effect by exposing rats and measuring arterial flow-mediated dilation (FMD) pre- and post-exposure. We measured FMD before and after inhalation of sidestream smoke from research cigarettes containing normal and reduced nicotine level with and without menthol, as well as 2 of the main aldehyde gases found in both smoke and e-cigarette aerosol (acrolein and acetaldehyde), and inert carbon nanoparticles. Results: FMD was reduced by all 4 kinds of research cigarettes, with extent of reduction ranging from 20% to 46% depending on the cigarette type. While nicotine was not required for the impairment, higher nicotine levels in smoke were associated with a greater percent reduction of FMD (41.1±4.5% reduction versus 19.2±9.5%; P =0.047). Lower menthol levels were also associated with a greater percent reduction of FMD (18.5±9.8% versus 40.5±4.8%; P =0.048). Inhalation of acrolein or acetaldehyde gases at smoke-relevant concentrations impaired FMD by roughly 50% ( P =0.001). However, inhalation of inert carbon nanoparticles at smoke-relevant concentrations with no gas phase also impaired FMD by a comparable amount ( P <0.001). Bilateral cervical vagotomy blocked the impairment of FMD by tobacco smoke. Conclusions: There is no single constituent or class of constituents responsible for acute impairment of endothelial function by smoke; rather, we propose that acute endothelial dysfunction by disparate inhaled products is caused by vagus nerve signaling initiated by airway irritation.