Possibility of downregulation of atrial natriuretic peptide receptor coupled to guanylate cyclase in peripheral vascular beds of patients with chronic severe heart failure.

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Abstract
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.