From rest to stressed: endothelin-1 levels in young healthy smokers and non-smokers

IntroductionEndothelin-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.MethodsHealthy 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 12 h 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.ResultsMean age was 28.6 ± 7.2 years and body mass index (BMI) was 23.6 ± 3.2 kg/m2. 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.ConclusionsAn 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.