It has been known since the first half of the twentieth century that atrial myocardiocytes contain secretory granules. However, it was demonstrated only in the years 1980/1990 that the heart also possesses an endocrine function because it synthesizes and secretes a family of peptide hormones, called cardiac natriuretic peptides, with a potent diuretic, natriuretic, and vasodilating action, as well as complex interactions with both the neurohormonal and immunological systems.

Natriuretic peptides constitute a complex family of inter related peptides that include ANP, BNP, CNP, urodilatin, and DNP. However, only ANP and BNP peptides are produced and secreted in appreciable amounts by the heart and, thus, deserve the definition of cardiac natriuretic peptides. Cardiac natriuretic peptides are produced as prepro-hormones (prepro- ANP and prepro-BNP), containing a signal peptide at the NH2-terminal level (Fig. 1). The respective pro- hormones (proANP and proBNP) are formed after the signal peptide’s enzymatic removal and stored in the secretory granules of myocells. The pro-hormones are then cleaved into two fragments upon release from the myocardiocyte: a longer one, comprising the NH2-terminal portion (termed NT-proANP and NT-proBNP), and a shorter COOH-terminal one, which constitutes the active hormone (ANP and BNP). The active hormones, ANP and BNP, have a faster plasma clearance than their respective propeptides, NT-proANP and NT-proBNP, and, consequently, lower circulating levels. Recent studies have also shown that proBNP is also present in the circulation (Fig. 1) and represents the predominant circulating peptide in patients with heart failure.

Fig1. The myocardiocyte’s production, secretion, and peripheral degradation of natriuretic-type B peptides (proBNP, BNP, and NT-proBNP). The active hormone BNP derives from a 108 amino acid precursor, called proBNP. ProBNP can be transformed by specific enzymes (chorin and furin) in the cytoplasm of myocardiocytes (car diac pool) and in the circulation (plasma pool) into two peptides, one longer NT-proBNP, inactive peptide, and one shorter BNP, the active hormone. These peptides, in turn, can be degraded by proteolytic enzymes into even shorter polypeptides. (Copyright EDISES 2021. Reproduced with permission)

The contractile and neuroendocrine functions of cardio myocytes are closely linked and influence each other through numerous complex feedback mechanisms, contributing together to determine cardiac function proper. Consequently, tests that assess contractile function (such as ECG and echo cardiography) and those that measure neurohormonal levels provide different but complementary information about cardiac function. These aspects should be evaluated separately using appropriate methods to better understanding the role of the heart in some complex clinical conditions, especially in heart failure.

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