Endocrine Paradox in Heart Failure: Resistance to Biological Effects of Cardiac Natriuretic Hormones

We read the interesting minireview by Goetze (1) concerning the biochemistry of pro-B-type natriuretic peptide (proBNP)-derived peptides: the main message is the potential clinical relevance of the proBNP-derived peptides, which should be considered for current clinical interpretation of plasma BNP concentrations and be the focus of ongoing research. Accordingly, the lack of accurate studies on in vivo production/secretion mechanisms and metabolism of BNP- and proBNP-related peptides explains the incomplete knowledge of the pathophysiologic significance of this hormone system. Thus, we agree with Goetze that deeper insight into the biochemistry of these peptides could pave the way for more sensitive and disease-specific assays in the clinical setting. We have some observations concerning the presence of an “endocrine paradox in heart failure” (1). The lack of encoding and processing of the precursor peptides to the mature hormones, atrial natriuretic peptide (ANP) and BNP, which have a potent diuretic and natriuretic effect, could explain the disturbed electrolyte and fluid homeostasis occurring in chronic heart failure (2)(3). However, the hypothesis of heart failure as a syndrome of cardiac natriuretic hormone (CNH) deficiency was challenged when this system was investigated in experimental animals and in humans. In fact, patients with congestive heart failure [New York Heart Association (NYHA) classes III–IV] have greatly increased plasma concentrations of CNHs compared with healthy individuals (up to 500-fold or more for plasma BNP concentration) (1)(2)(3). Goetze (1) tries to explain this paradox of heart failure (i.e., highly increased CNH concentrations in patients with sodium retention) by suggesting that a part of circulating CNH-related peptides (especially proBNP-related peptides) is not biologically active. We agree that increased concentrations of immunoreactive, but biologically inactive, proBNP-related peptides (as well as proANP-related peptides) are present in patients with heart failure. As also correctly pointed out in the … [↵][1]aAddress correspondence to this author at: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. Fax 45-35454640; e-mail jpg{at}dadlnet.dk. [1]: #xref-corresp-2-1