Abnormal neurohumoral responses to exercise in patients with heart disease: inhibition of an increase in endothelin-1 production during exercise.
We have reported that the plasma endothelin-1 (ET-1) level is significantly increased by exercise in healthy athletes and that it is elevated in the circulation of the non-working leg but not the working leg, suggesting that ET-1 plays an important role in redistribution of blood during exercise. This study was designed to compare alterations of neurohumoral substances by exercise in normal subjects and patients with heart disease. Study patients comprised three groups: eight patients with congestive heart failure (CHF) due to Ebstein's anomaly or single-ventricle heart after Fontan operation; six patients with complete transposition of the great arteries (TGA) after an anatomic surgical correction who may be candidates for ischemic heart disease; and five age-matched normal subjects. All patients were in New York Heart Association functional class I. All subjects performed symptom-limited treadmill exercise. It is suggested that patients with CHF or TGA have a manifest or latent exercise intolerance, respectively. In failed to increase plasma ET-1 level, although it caused a greater increase in norepinephrine, angiotensin II, and arginine vasopressin than in the controls. Exercise also caused a delay in the increased response of plasma ET-1 levels in patients with TGA after an anatomic surgical repair. On the other hand, plasma brain natriuretic peptide (BNP) level was augmented by exercise in patients with CHF and patients with TGA but not in the controls. The present results suggest that an increase in ET-1 production during exercise is absent in patients with heart disease. The mechanisms of inhibition of ET-1 production during exercise in patients with heart disease remain to be elucidated. However, the present study suggests that ET-1 plays an important role in redistribution of blood during exercise, and proposes the possibility that failure of an increase in ET-1 production results in exercise intolerance in patients with heart disease.
Ishikawa
S
S
Department of Pediatric Cardiology, Fukuoka Children's Hospital, Japan.
Miyauchi
T
T
Ueno
M
M
Sagawa
K
K
Sakai
S
S
Ushinohama
H
H
Kado
H
H
Sunagawa
H
H
Goto
K
K
Sugishita
Y
Y
Honda
S
S
D002648:Child; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000097:blood; D015444:Exercise / Q000502:physiology*; D006330:Heart Defects, Congenital / Q000150:complications / Q000378:metabolism*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011659:Pulmonary Gas Exchange; D014188:Transposition of Great Vessels / Q000378:metabolism
D019332:Endothelin-1; D018377:Neurotransmitter Agents