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As early as 1976, in the preface to the first edition of his popular monograph on the physiology of the heart, Arnold M. Katz pointed out:

“...Although it remains fashionable to consider the heart as a muscular pump, this organ is much more than a hollow viscus that provides mechanical energy to propel blood through the vasculature. It is an intricate biological machine that contains, within each cell, a complex of control and effector mechanisms...” [].

In classical physiology, the function of the heart is described as the target of autonomic nervous system modulation superimposed on a mechanistic regulation. The aim of this chapter is to remind us of the basic knowledge in this field, as a bridge to the thorough description of the physiological and clinical relevance of the discovery of cardiac endocrine function. An extensive review of the current physiological view of cardiovascular function is beyond the scope of this book and can be found in several excellent textbooks [, ].

The aim of this Chapter is to summarize the most recent issues on the production, secretion, biological activity and metabolism of CNH. The hypotheisis that natriuretic peptides constitute a family sharing endocrine, paracrine and autocrine actions and neurotransmitter and immunomodulator functions closely related to the other regulatory systems (nervous, endocrine and immunological) in a biological hierarchical network will be discussed with particular emphasis. Finally, such as an example to support this hypothesis, the integrated action of CNH system during pregnancy and fetal life as well as in the regulation of vascuar system wil be illustrated in detail.

Cardiac natriuretic hormones (CNH) constitute a complex family of related peptides with similar peptide chains as well as degradation pathways (see Chap. 3 for more details). CNH derive from common precursors, pre-pro-hormones (i.e., preproANP and preproBNP). Pro-hormone peptides are further split into an inactive longer NT-proANP or NTproBNP and the biologically active hormones, ANP or BNP, which are secreted in the blood in equimolar amounts. However, ANP and BNP have a shorter plasma half-life and consequently lower plasma concentrations compared to NT-proANP and NT-proBNP (Table 4.1). For these reasons, setting up an immunoassay for N-terminal peptide fragments of proANP and proBNP should be easier than that for ANP and BNP, because the requested analytical sensitivity is not too low []. However, immunoassays for NTproANP and NTproBNP may be affected by problems related to the different assay specificities: as shown in Table 4.1, different results are produced by different methods with a large bias [–]. The different analytical performances could have some relevance in the diagnostic accuracy of different assay methods in discriminating between subjects with or without cardiac disease [–].

CNH are powerful hormones with important physiological effects. Consequently, by considering their assay only as a marker for cardiac disease may result in a misinterpretation or underestimation of their biological action and of their pathophysiological role in cardiovascular as well as other diseases. In the first part of Chapter 5 (from section 5.1.1 to 5.1.5), some physiological conditions in which the interpretations of increased levels of CNH may be difficult or provoke misunderstanding will be discussed in detail. In particular, the influence of age and sex hormones on circulating levels of CNH will be reviewed (section 5.1.1). As far as the clinical interpretation of variations of circulating levels of CNH is concerned, some important points will be stressed: 1) the pathophysiological and clinical consequence of the progressive resistance to biological actions of CNH in patients with heart failure (section 5.1.3); 2) the inter-relationship between hemodynamic mechanisms and activity of neuro-endocrine system in determining the variation of circulating levels of CNH (section 5.1.4); 3) the clinical relevance of variation of CNH levels (section 5.1.5). The discussion of these points will lay the pathophysiological foundations for better understanding of the second part of this Chapter, which concerns the diagnostic and prognostic role of CNH assay in patients with cardiovascular disease (sections from 5.2 to 5.5).

The CNH assay may be clinically useful in many other conditions besides cardiovascular diseases [, ]. The list of clinical conditions with altered (increased or decreased compared to normal range) circulating levels of CNH must be continuously updated because of the huge amount of data accumulating in this field every day (see Table 5.1).

Heart failure is a life-threatening cardiovascular disease that is increasing in prevalence in North America and Europe [–]. It is a common cause of death and is accompanied by high direct and indirect costs for treatment. The current situation faced by patients and the medical community with regard to this problem is one of high mortality, repeated hospitalizations, and combination therapies. The different classes of pharmacological agents that are currently used for patients suffering from heart failure include angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers, aldosterone antagonists, β-blockers, digitalis, diuretics, inotropic agents, nitrates, and vasodilators [–]. While these agents are all important therapeutic tools, the prognosis for patients with heart failure remains poor [–].

“Deep in my heart” something different from contractile proteins and equally fundamental for the biology of human beings has been described.