Physiological role of endothelin-1 in nonworking muscles during exercise in healthy subjects

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. However, the role of ET-1 in exercise-induced physiological responses is still to be investigated. The purpose of the present study was to investigate in healthy volunteers whether the ET-1 plasma concentration in nonworking muscles is changed by exercise and to investigate the physiological role of ET-1 during exercise. Bicycle ergometer cardiopulmonary exercise tests were performed in 36 healthy men (mean age, 22.5 years). Blood samples for measuring ET-1 were drawn from the cubital vein during rest and immediately after the exercise test. The ET-1 change ratio was calculated as ET-1 immediately following exercise/ET-1 during the resting state. Cardiac output (CO) was measured during the exercise test by the impedance method. Arterial venous oxygen difference (AVO2D) when CO reached 10L/min or 15L/min was calculated as AVO2D = VO2/CO. Results were as follows: (1) the ET-1 change ratio correlated inversely with exercise time at the anaerobic threshold (r = -0.37, p = 0.03) and peak exercise time (r = -0.35, p = 0.04); (2) the ET-1 change ratio tended toward an inverse correlation with deltaVO2/deltawork rate (r = -0.29, p = 0.09); (3) the ET-1 change ratio correlated positively with AVO2D when CO reached 10L/min (r = 0.42, p = 0.02) and tended toward a positive correlation with AVO2D when CO reached 15 L/min (r = 0.32, p = 0.08). These results indicate that an increase in ET-1 in nonworking muscles may participate in the exercise-induced redistribution of blood flow and in increasing the blood flow to working muscles.