Circulation, Vol 85, 510-517, Copyright © 1992 by American Heart Association
DJ Stewart, P Cernacek, KB Costello and JL Rouleau
BACKGROUND. The possible contribution of endothelin-1, a potent
endothelium-derived vasoconstrictor peptide, to neurohumoral compensation
for hemodynamic stress was examined in nine normal volunteers and six
patients with severe congestive heart failure. METHODS AND RESULTS. Plasma
levels of endothelin-1 were measured with a sensitive and specific
radioimmunoassay. Venous blood samples were obtained after 90 minutes of
supine rest and serially during 30 minutes of 60 degrees upright tilt.
Endothelin-1 levels were compared with those of known neurohumoral
mediators of compensation. In normal subjects, the resting levels of
endothelin-1 were low (0.74 +/- 0.11 pg/ml), and there was a rapid increase
to 1.37 +/- 0.07 pg/ml at 5 minutes of upright tilting (p less than 0.05).
This increase was not sustained at 10 and 15 minutes of tilt, but there was
a trend toward a second rise at 30 minutes (1.14 +/- 0.17 pg/ml; p = 0.06).
This biphasic pattern of response was shared by dopamine and reflected the
response of systemic blood pressure to postural change. In contrast, slower
and more sustained increases in circulating levels were observed for
norepinephrine, epinephrine, aldosterone, plasma renin activity, and
vasopressin, whereas atrial natriuretic peptide tended to decrease
progressively. Patients with congestive heart failure had markedly higher
basal levels of circulating endothelin-1 than normal subjects (3.7 +/- 0.5
pg/ml; p less than 0.01), and there was no further increase on postural
change. Similar patterns were observed for the other neurohumoral mediators
measured, with the degree of blunting of the response to upright tilting in
heart failure being inversely related to the magnitude of increase in basal
levels. CONCLUSIONS. Alterations in plasma levels of endothelin in
congestive heart failure and in response to postural change were
qualitatively and quantitatively similar to the alterations of known
mediators of neurohumoral compensation. In addition, the increase in plasma
endothelin-1 during upright tilting in normal subjects preceded the
increases in circulating levels of the other vasoconstrictor mediators,
consistent with a role of endothelin-1 in neurohumoral compensation for
hemodynamic stress.
ARTICLES
Elevated endothelin-1 in heart failure and loss of normal response to postural change
McGill Unit for the Prevention of Cardiovascular Disease, McGill University Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.
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