environmental toxicology and pharmacology 31 ( 2 0 1 1 ) 453–459 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/etap Role of carbon monoxide in impaired endothelial function mediated by acute second-hand tobacco, incense, and candle smoke exposures Lynn P. Weber a,b,∗ , Ahmad Al-Dissi a , Jordan S. Marit b , Timothy N. German b , Sharilyn D. Terletski b a Toxicology Graduate Program, University of Saskatchewan, Saskatoon, SK, Canada b Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, Canada article info Article history: Received 22 November 2010 Received in revised form 18 February 2011 Accepted 21 February 2011 Available online 26 February 2011 Keywords: Tobacco Candle smoke Incense smoke Endothelial dysfunction Flow-mediated dilation Blood gases Carbon monoxide abstract The aim of this study was to determine if carbon monoxide (CO) is responsible for acute adverse cardiovascular effects of different sources of smoke: second-hand tobacco smoke (SHS), incense and candle smoke. Endothelial function was tested using flow-mediated dilation (FMD) in pigs and was shown to be sensitive to nitric oxide synthase blockade. Subse- quent experiments showed that FMD was significantly impaired compared to sham-exposed pigs at 30 min after a 30-min exposure to all three sources of smoke. In contrast, SHS signif- icantly increased systolic, diastolic and pulse pressures compared to sham-exposure, while both incense and candle smoke exposure had no effect. The FMD impairment correlated well with CO levels in the exposure chamber, but not total particulates or venous CO–hemoglobin. Therefore, this study suggests a gas phase component of smoke that accompanies CO, but not CO itself, is responsible for acute endothelial dysfunction after SHS, incense or candle smoke exposure. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Cardiovascular disease is the leading cause of death in the developed world (Yach et al., 2004). Impaired endothelial func- tion caused by oxidative stress-mediated inactivation of nitric oxide is thought to be an early event in cardiovascular disease pathogenesis (Versari et al., 2009; Harris et al., 2010), leading to elevated blood pressure, increasing myocardial demand and promoting atherogenesis (Versari et al., 2009). Epidemiolog- Abbreviations: FMD, flow-mediated dilation; CO, carbon monoxide; Hb, hemoglobin; SHS, second-hand smoke; l-NAME, l-N(G)-nitro- l-arginine methyl ester. ∗ Corresponding author at: Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, Canada S7N 5B4. Tel.: +1 306 966 8734; fax: +1 306 9667376. E-mail address: lynn.weber@usask.ca (L.P. Weber). ical studies have established that exposure to second-hand tobacco smoke (SHS) and outdoor air pollution are signif- icant risk factors for cardiovascular disease (Lewtas, 2007; Liu et al., 2009). However, SHS and air pollution arising from outdoor sources such as vehicle exhaust are also the major contributors to high particulate pollution in indoor environ- ments (Lewtas, 2007; Arhami et al., 2010). In addition to vehicle exhaust and SHS, burning wood or any other combustible material indoors has also been shown to contribute to indoor air pollution (Barregard et al., 2006; Bräuner et al., 2008). 1382-6689/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.etap.2011.02.008