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 two of the main aldehyde gases found in both smoke and e-cigarette acrolein (acrolein and acetaldehyde), and inert carbon nanoparticles. Results: FMD was reduced by all four kinds of research cigarettes, with the extent of reduction ranging from 20–46% 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% percent reduction vs. 19.2±9.5%; p=0.047). Lower menthol levels were also associated with a greater percent reduction of FMD (18.5±9.8% vs. 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.

Raw ultrasound data were collected by a 35 MHz ultrasound transducer (Vevo660 and Vevo 3100 LT; VisualSonics, Toronto, Canada). Ultrasound images were processed using an automated system (Brachial Analyzer; Medical Imaging Applications, Coralville, IA).

Use VisualSonics Vevo software for viewing .vsi images and Brachial Analyzer for diameter measurements.