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Circulation, Vol 87, 70-75, Copyright © 1993 by American Heart Association
T Tsutamoto, T Kanamori, N Morigami, Y Sugimoto, O Yamaoka and M Kinoshita
BACKGROUND. High levels of endogenous atrial natriuretic peptide (ANP) are
thought to compensate the condition of patients with heart failure by
reducing preload and afterload. However, recent reports have indicated that
a high plasma ANP level is a prognostic predictor in patients with heart
failure. Therefore, the role of endogenous ANP has not been clearly
established in patients with heart failure. METHODS AND RESULTS. The plasma
ANP and cGMP levels were determined in the femoral artery and the femoral
vein of 97 patients with chronic congestive heart failure (CHF). The plasma
ANP level decreased significantly, whereas the plasma cGMP levels increased
significantly from the femoral artery to the femoral vein. Among patients
with mild CHF (n = 52), the plasma cGMP level correlated with the ANP
level, and the calculated ANP extraction level also correlated with the
calculated cGMP production in the peripheral circulation (r = 0.70, p <
0.001). In contrast, these correlations were not found in patients with
severe CHF (n = 45). Among these patients, the plasma cGMP levels seemed to
reach a plateau despite high levels of plasma ANP, and the molar ratio of
cGMP production to ANP extraction in the peripheral circulation was
significantly lower than in patients with mild CHF (36.7 +/- 9.5 versus 183
+/- 17, p < 0.001). In patients with acute severe CHF (n = 9) and those
with mild CHF, patients who were administered exogenous ANP, plasma cGMP
levels increased in proportion to those of plasma ANP without saturation.
CONCLUSIONS. These results indicate that downregulation of ANP receptors
coupled to guanylate cyclase may occur in the peripheral vascular beds of
patients with chronic severe CHF.
ARTICLES
Possibility of downregulation of atrial natriuretic peptide receptor coupled to guanylate cyclase in peripheral vascular beds of patients with chronic severe heart failure
First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
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