Effects of Prolonged Strenuous Exercise on Plasma Levels of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Healthy Men

Haruo Ohba, MD,a Hideomi Takada, MD,b Haruki Musha, MD,c Junzo Nagashima, MD,a Narumi Mori, MD,b Toru Awaya, MD,a Kazuto Omiya, MD,a and Masahiro Murayama, MD a; Kawasaki and Yokohama, Japan.


Am Heart J. 2001;141(5) 

In This Article

Abstract and Introduction

Background: Now that marathon racing is growing in popularity, many thousands of enthusiastic athletes are participating in various ultramarathons all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has been widely used for clinical evaluation of cardiac dysfunction. However, little is known about the response of plasma BNP to prolonged strenuous exercise. We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP.
Methods: Levels of plasma ANP, BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage.
Results: Whereas all variables significantly increased after the race, increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels. The cTnT level after the race was greater than the upper reference limit in 9 of 10 men.
Conclusions: Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.

Atrial natriuretic peptide (ANP), composed of 28 amino acid residues, was isolated from human atria by Kangawa and Matsuo[1] in 1984. The major portion of plasma ANP is synthesized in and secreted from atria and plays an important role in body fluid and cardiovascular homeostasis as a cardiac hormone with a wide range of potent biological effects, including natriuresis, diuresis, and vasodilation.[1,2,3] The second cardiac hormone, brain natriuretic peptide (BNP), was first isolated from the porcine brain by Sudoh et al[4] in 1988. Thereafter, it was demonstrated that plasma BNP was predominantly synthesized in and secreted from the heart, mostly from the ventricles,[5,6,7] and that human BNP is composed of 32 amino acid residues.[8] BNP has a striking similarity to ANP both in structure and in peripheral and central actions.[1,2,3,4,8,9,10] The accumulation of recent findings about these cardiac natriuretic peptides has revealed clinically instructive information in the field of cardiology. The plasma level of BNP at rest in normal individuals is lower than that of ANP.[7,11,12] On the other hand, plasma levels of ANP and BNP markedly increase in patients with heart failure in proportion to its severity,[7,11,12,13,14,15,16,17,18,19] and the BNP level surpasses the ANP level in severe cases.[7,18] Furthermore, as for the responses of plasma ANP and BNP levels to exercise in patients with heart failure, it has been shown that ANP and BNP values after exercise were significantly elevated compared with at-rest values and that the BNP level both at rest and after exercise had a significantly negative correlation with left ventricular ejection fraction.[20] On the basis of this accumulated information, plasma concentration of the natriuretic peptides, especially BNP, could be considered as a sensitive marker for left ventricular dysfunction. In fact, measurement of plasma BNP concentration has been widely used for clinical evaluation of left ventricular function in patients with heart failure. Also, in the early phase of acute myocardial infarction (AMI), it has been confirmed that these cardiac hormones, particularly BNP, remarkably and significantly increase and that the elevated BNP level is useful for estimating the degree of left ventricular dysfunction,[21,22,23,24] the degree of left ventricular remodeling,[22,27] and long-term prognosis.[26]

In healthy individuals, the plasma level of ANP has been shown to significantly increase after not only short-term exercise[28,29,30] but also after endurance exercise.[31,32] To some extent, this accumulation of recent findings has revealed the stimuli for ANP release on exercise. Among these, sympathetic nervous excitation, intensity of exercise, and age of the examinee have been reported as either stimuli or factors related to the release of ANP on exercise.[28,29,30,31,32,33,34,35] On the other hand, the response of the plasma BNP level to exercise in healthy individuals remains controversial. Although some recent studies showed a tendency toward an increase in BNP after short-term exercise (without statistical significance),[35,36] an opposing report showed no such change.[20] However, the response of BNP to prolonged strenuous exercise has not been examined.

Marathon running is growing in popularity, and many thousands of enthusiastic athletes are participating in various ultramarathon races such as 100-km runs all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. Transient cardiac dysfunction after prolonged strenuous running, what is called "cardiac fatigue," has been reported in healthy athletes.[37,38] Furthermore, several recent reports that used cardiospecific biochemical markers, cardiac troponin T (cTnT)[39,40,41,42] and cardiac troponin I (cTnI),[43] which are highly specific and sensitive to myocardial cell necrosis, showed the occurrence of subclinical and irreversible myocardial injury during a long-distance road race in healthy runners.[44,45,46,47,48]

If "cardiac fatigue" or myocardial injury after exhaustive exercise does occur, even at subclinical levels, plasma BNP should increase after such exercise. Also, BNP should more sensitively respond to cardiac dysfunction or myocardial cell necrosis than ANP. In other words, we should be able to confirm the presence of minimal cardiac dysfunction or myocardial injury by means of measurement of plasma BNP.

In this context, this study was designed with two objectives. The first aim was to investigate the response of plasma levels of ANP and BNP, with a particular focus on the latter, to a 100-km ultramarathon in amateur male athletes, being regarded as healthy individuals, and to identify the stimuli for the release of these natriuretic peptides on such exercise. As a second aim of the study, we examined the correlations between the changes before and after the race in each of the two cardiac hormones, with changes in cTnT as a marker for myocardial cell necrosis during the race.


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