Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones

Abstract

Clerico A, Giannoni A, Vittorini S, Passino C. Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones. Am J Physiol Heart Circ Physiol 301: H12-H20, 2011. First published May 6, 2011; doi:10.1152/ajpheart.00226.2011 reported that atrial extracts contain some biologically active peptides, which promote a rapid and massive diuresis and natriuresis when injected in rats. It is now clear that the heart also exerts an endocrine function and in this way plays a key role in the regulation of cardiovascular and renal systems. The aim of this review is to discuss some recent insights and still-debated findings regarding the cardiac natriuretic hormones (CNHs) produced and secreted by cardiomyocytes (i.e., atrial natriuretic peptide and B-type natriuretic peptide). The functional status of the CNH system depends not only on the production/secretion of CNHs by cardiomyocytes but also on both the peripheral activation of circulating inactive precursor of natriuretic hormones and the transduction of the hormone signal by specific receptors. In this review, we will discuss the data supporting the hypothesis that the production and secretion of CNHs is the result of a complex integration among mechanical, chemical, hemodynamic, humoral, ischemic, and inflammatory inputs. The cross talk among endocrine function, adipose tissue, and sex steroid hormones will be discussed more in detail, considering the clinically relevant relationships linking together cardiovascular risk, sex, and body fat development and distribution. Finally, we will review the pathophysiological role and the clinical relevance of both peripheral maturation of the precursor of B-type natriuretic peptides and hormone signal transduction.B-type natriuretic peptide; sex steroids; adipokines; heart failure; cardiovascular risk THIRTY YEARS AGO, De Bold et al. (20) reported that atrial extracts contain some biological active peptides, which promote a rapid and massive diuresis and natriuresis when injected in rats. Several endogenous peptide hormones with natriuretic and vasodilator activity have been identified in the human blood and peripheral tissues (3,30,69,85,86). Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their related peptides are predominantly produced by atrial and ventricular cardiomyocytes. The term "cardiac natriuretic hormones" (CNHs) will be used in this review to indicate these two families of natriuretic peptides. Another natriuretic peptide, named C-type natriuretic peptide (CNP), is predominantly produced by the endothelial cells, including those of cardiac vessels. Finally, urodilatin is an NH 2 -terminal (NT) 4-amino acid (aa) extented form of ANP, which is produced by the same ANP gene and secreted into the urine by renal tubular cells (16,34,69).From the original observations made 30 years ago, the advances in this particular research field have determined a complete revision about the role of the heart. It is now clear that the heart also exerts a...

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

“…From a pathophysiological viewpoint, it is important to note that the opposite actions of male and female gendersteroid hormones may explain the difference in circulating levels of natriuretic peptides and cTn. Indeed, male steroid hormones may have an anabolic effects on cardiac cells (inducing cardiac hypertrophy) [144], but also an inhibitory action on the production of cardiac natriuretic hormones [145,146]; female gender steroid hormones may have anti-proliferative effects on myocardiocytes [144], but stimulate the production/secretion of cardiac natriuretic peptides [145,146].…”

New issues on measurement of B-type natriuretic peptides

“…On the contrary, the decrease in NT-proBNP levels should reflect the beneficial effects of the drug on myocardial function and vascular hemodynamics, especially because of the inhibition in renin-angiotensin-aldosterone system activity [11,13]. Indeed, the reduction of cardiac stress during LCZ696 treatment should reduce the production and secretion of natriuretic peptides from cardiomyocytes, hence producing a fall in circulating levels of NTproBNP, too [14]. Considering these pathophysiological premises, clinicians should accurately evaluate the clinical setting in order to correctly interpret the variations of natriuretic peptides, measured by commercially available laboratory methods.…”

“…In particular, clinicians should take into account that an increase in BNP levels in HF patients could be caused by inhibiting effect of LCZ696, but also by deterioration of clinical conditions in patients who do not respond to treatment. On the other hand, an increase in plasma NT-proBNP is usually due to deterioration of clinical conditions of HF patients [1,14].…”

“…After only few years, several endogenous peptide hormones with natriuretic and vasodilator activity have been identified in the human blood and peripheral tissues [1,14]. Atrial natriuretic peptide (ANP), BNP and their related peptides are predominantly produced by atrial and ventricular cardiomyocytes, constituting the cardiac endocrine function [14].…”

Preoperative B-type natriuretic peptides in patients undergoing noncardiac surgery: a cumulative meta-analysis

“…However, over the last 10 years, 1 multiple studies have examined the ability of preoperative B-type natriuretic peptides (NP) (i.e. B-type natriuretic peptide [BNP] or N-terminal fragment of proBNP [NT-proBNP]), which are released from cardiac myocytes and fibroblasts in response to myocardial stretch, ischaemia and other neuro-endocrine stimuli, 2,3 to predict these events.…”