Exhaustive exercise-induced tissue hypoxia does not change endothelin and big endothelin plasma levels in normal volunteers

Chronic hypoxia has been shown to increase plasma endothelin levels. The current study was undertaken to examine the effect of exercise-induced tissue hypoxia on plasma levels of endothelin-1 (ET-1) and its precursor big endothelin-1 (Big-ET-1). After approval by the local ethical committee an incremental dynamic exercise test was performed in 12 physically trained volunteers (aged 20 to 40 years), using an electrically braked bicycle ergometer. The protocol included a step-wise increase of the workload until a heart rate of 130/min was reached, followed by a maintenance period of 25 min, and a further step-wise increase until exhaustion. Blood was drawn before, at several time points during, and 5 min after termination of the study for determination of ET-1, Big-ET-1, plasma renin activity (PRA), angiotensin converting enzyme (ACE), norepinephrine, epinephrine, and lactate. Lactate levels at baseline were 14.5 ± 1.6 mg/dL (mean ± SEM), which increased to 76.5 ± 4.8 mg/dL at the time of exhaustion (P< .01). Baseline values for ET-1 and Big-ET-1 were 0.264 ± 0.061 and 0.637 ± 0.130 fmol/ml, respectively, which remained essentially unaltered throughout the exercise test. PRA was 1.46 ± 0.45 ng/mL/h before exercise and increased to 3.55 ± 0.96 ng/mL/h at exhaustion (P< .001). Norepinephrine and epinephrine were also increased at exhaustion. The study demonstrates that exhaustive physical exercise with acute development of pronounced tissue hypoxia—in contrast to chronic hypoxia—does not influence the release of ET-1 or Big-ET-1 or the conversion of the precursor to the active compound. Unlike endothelin, circulating renin and the catecholamines were markedly stimulated by this maneuver.