title: From rest to stressed: endothelin-1 levels in young healthy smokers and non-smokers.
abstract: BACKGROUND
  Endothelin-1 (ET-1) is a potent vasoconstrictor produced by vascular endothelial cells, and a known marker of endothelial dysfunction. However, the acute and chronic effects of smoking and nicotine gum on the ET-1 response to acute physical stress in young healthy smokers have not been investigated.
  
  
  METHODS
  Healthy smokers (n=35) and non-smokers (n=35) underwent an exercise test to exhaustion (maximal oxygen consumption) on a treadmill. Smokers were assessed a) after 12h smoking abstinence (termed chronic smoking), b) immediately after smoking one cigarette (termed acute smoking), and c) immediately after chewing nicotine gum. Blood was drawn immediately pre-exercise, and 3 minutes post-exercise. During exercise, cardiorespiratory parameters were obtained breath-by-breath using an automated metabolic cart. Plasma ET-1 levels were quantified using enzyme-linked immunosorbent-assay. The above protocol was designed to incorporate exercise as a vascular stressor to reveal changes that would not be detected at rest.
  
  
  RESULTS
  Mean age was 28.6±7.2 years and body mass index (BMI) was 23.6±3.2 kg/m(2). Post-exercise ET-1 levels were significantly lower than pre-exercise levels in non-smokers (P<0.001) and smokers under all three conditions (P=0.005, P<0.001, P=0.001, respectively). There were no differences in post-exercise ET-1 levels between non-smokers and smokers under all three conditions, however the absolute and relative decrease in ET-1 levels was significantly smaller in chronic smokers compared with non-smokers (P=0.007 and P=0.004). Chronic smokers had a significantly lower exercise-induced change in tidal volume (P=0.050), fraction of expired CO2 (P=0.021), oxygen consumption (P=0.005), carbon dioxide elimination (P=0.004) and peak expiratory flow (P=0.003) compared with non-smokers. Furthermore, the decrease in ET-1 observed in non-smokers in response to exercise was significantly associated with exercise induced-changes in inspiratory time, time for a tidal volume cycle, respiratory frequency, inspired minute ventilation and peak inspiratory flow.
  
  
  CONCLUSIONS
  An acute decrease of circulating ET-1 in response to acute maximal exercise in young healthy individuals was noted. Chronic smokers had a significantly diminished decrease in ET-1 compared with non-smokers, however there were no significant differences in the ET-1 response between smokers under the three smoking conditions. Smokers were not able to achieve the same exercise-induced changes in cardiorespiratory parameters as non-smokers. By incorporating exercise as a vascular stressor in our study, we have taken a novel approach to provide evidence of an altered ET-1 and cardiorespiratory response that would not otherwise be observed at rest in young active healthy smokers.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3A 1A3, Canada.
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Cooke
authors.affiliation: Division of Internal Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, Montreal, Quebec, H3G 1A4, Canada.
authors.forename: Eirini
authors.initials: E
authors.lastname: Toli
authors.affiliation: Division of Internal Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, Montreal, Quebec, H3G 1A4, Canada.
authors.forename: Yessica-Haydee
authors.initials: YH
authors.lastname: Gomez
authors.affiliation: Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3A 1A3, Canada.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Mutter
authors.affiliation: Division of Cardiology, Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3G 1Y6, Canada; Division of Clinical Epidemiology, Department of Medicine, Faculty of Medicine, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Eisenberg
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA; VA Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
authors.affiliation: Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3A 1A3, Canada; Division of Internal Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, Montreal, Quebec, H3G 1A4, Canada. Electronic address: stella.daskalopoulou@mcgill.ca.
authors.forename: Stella S
authors.initials: SS
authors.lastname: Daskalopoulou
mesh_terms: D000328:Adult; D015308:Anaerobic Threshold / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D002638:Chewing Gum; D019332:Endothelin-1 / Q000097:blood*; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D015656:Respiratory Mechanics / Q000187:drug effects; D012146:Rest / Q000502:physiology*; D012907:Smoking / Q000097:blood*; D013315:Stress, Psychological / Q000097:blood*; D055815:Young Adult
chemical_list: D002638:Chewing Gum; D019332:Endothelin-1; D018722:Nicotinic Agonists; D002245:Carbon Dioxide; D009538:Nicotine
keywords: Endothelin-1; Endothelium; Exercise; Nicotine; Smoking