Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events.

A trial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are the known members of the mammalian natriuretic peptide system. The discovery of natriuretic peptides (NPs) dates back to 1981, when de Bold et al. found that administration of atrial extracts into intact rats causes diuresis and natriuresis. In 1983–1984, ANP was then isolated and purified, and the amino acid sequence was determined in rats and humans. Whereas atrial ANP levels are higher than those in ventricles, the ventricular myocardium becomes a major source for circulating ANP in failing hearts owing to larger mass. In 1988, a homologous peptide with similar biological activities was isolated from porcine brain and named BNP. BNP is expressed in both adult atria and ventricles, but is mainly released from the ventricles. The key stimulant for release of ANP and BNP from the heart is myocardial stretch, whereas the third family member, CNP, is mainly released from endothelial cells in response to various cytokines as depicted in Figure 1. Classically, ANP and BNP exert diuretic, natriuretic, and hypotensive actions, and genetic variations of the NPPA-NPPB locus that increase the circulating levels of ANP and BNP in patients have been shown to offer protection from hypertension. In the clinical setting, analysis of serum levels of ANP and BNP is used for diagnosis of heart failure (HF) and it has also been suggested that analysis for circulating levels of ANP and BNP may be useful in monitoring the efficacy of therapies in treatment of patients with HF. Notably, though, treatment of patients with b-blockers, which reduces cardiovascular morbidity and mortality especially in post-MI (myocardial infarction) patients, is associated with elevated circulating levels of ANP and BNP. Recombinant human ANP and BNP have been approved for treatment of acutely decompensated congestive HF in Japan and the United States, respectively. In addition to renal effects, during the last decade it has become evident that NPs have direct effects in multiple other tissues and are involved in regulation of a variety of biological processes, such as cardiac hypertrophy, fibrosis, metabolism, angiogenesis, and cardiomyocyte viability. In this review, we summarize the recent findings of the cardiovascular effects of NPs with emphasis on effects of NP signaling on cardiac structure and function.