Natriuretic Peptides and Cardiometabolic Health

Abstract

Natriuretic peptides are cardiac-derived hormones with a range of protective functions, including natriuresis, diuresis, vasodilation, lusitropy, lipolysis, weight loss, and improved insulin sensitivity. Their actions are mediated through membrane-bound guanylyl cyclases that lead to production of the intracellular second-messenger cyclic guanosine monophosphate. A growing body of evidence demonstrates that genetic and acquired deficiencies of the natriuretic peptide system can promote hypertension, cardiac hypertrophy, obesity, diabetes mellitus, the metabolic syndrome, and heart failure. Clinically, natriuretic peptides are robust diagnostic and prognostic markers, and augmenting natriuretic peptides is a target for therapeutic strategies in cardiometabolic disease. This review will summarize current understanding and highlight novel aspects of natriuretic peptide biology.

Figure 1

The post-translational processing of natriuretic peptides. From Volpe M, Rubattu S, Burnett J, Jr. Natriuretic peptides in cardiovascular diseases: Current use and perspectives. Eur Heart J. 2014;35:419–425. (Permission pending) Caption: Natriuretic peptide protein sequences and post-translational processing cleavage and degradation sites. NEP = neprilysin, DPPIV = dipeptidyl peptidase IV, IDE = insulin degrading enzyme.

Figure 2

The natriuretic peptide system responds to hemodynamic and metabolic stimuli through activation of guanylyl cyclase receptors resulting in cardiometabolic protect effects. From Volpe M, Rubattu S, Burnett J, Jr. Natriuretic peptides in cardiovascular diseases: Current use and perspectives. Eur Heart J. 2014;35:419–425. (Permission pending) Caption: Cardiomyocytes and endothelial cells are stimulated to release natriuretic peptides, which bind receptors with guanylyl cyclase activity. This activation leads to increased intracellular cyclic GMP with beneficial downstream effects mediated through protein kinase G and phosphodiesterase. CNP also inhibits adenylate cyclase to reduce cAMP levels through the natriuretic peptide receptor-C.

Figure 3

Natriuretic peptides as novel therapeutic targets in cardiometabolic disease. Adapted from Volpe M, Rubattu S, Burnett J, Jr. Natriuretic peptides in cardiovascular diseases: Current use and perspectives. Eur Heart J. 2014;35:419–425. (Permission pending) Caption: Natriuretic peptides exert beneficial effects on cardiac and vascular function directly and through inhibition of the renin-angiotensin-aldosterone axis and sympathetic nervous systems, making them ideal and novel targets for cardiovascular protection.