Abstract
The characterization of the cardiac hormone atrial natriuretic peptide (ANP99–126), synthesized and secreted predominantly by atrial myocytes under stimulation by mechanical stretch, has established the heart as an endocrine organ with potent natriuretic, diuretic, and vasodilating actions. Three additional distinct polypeptides resulting from proteolytic cleavage of proANP have been identified in the circulation in humans. The mid-sequence proANP fragment 31–67 (also known as proANP31–67) has unique potent and prolonged diuretic and natriuretic properties. In this review, we report the main effects of this circulating hormone in different tissues and organs, and its mechanisms of actions. We further highlight recent evidence on the cardiorenal protective actions of chronic supplementation of synthetic proANP31–67 in preclinical models of cardiorenal disease. Finally, we evaluate the use of proANP31–67 as a new therapeutic strategy to repair end-organ damage secondary to hypertension, diabetes mellitus, renal diseases, obesity, heart failure, and other morbidities that can lead to impaired cardiac function and structure.
Highlights
Natriuretic PeptidesThe human natriuretic peptides (NPs) consist of a family of three known peptides encoded in the human genome, with each being a distinct gene product with similar structure (Figure 1)
The atrial natriuretic peptide (ANP99−126), a hormone synthesized and secreted predominantly by cardiac cells, was the first member of the NP family to be discovered in de Bold et al (1981), and established the heart as an endocrine organ
Others and we have previously demonstrated the existence of a deficiency state of the endogenous biologically active NPs system in heart failure (HF) patients starting with the early stage of HF (Hawkridge et al, 2005; Belluardo et al, 2006; Niederkofler et al, 2008; Macheret et al, 2012)
Summary
Natriuretic PeptidesThe human natriuretic peptides (NPs) consist of a family of three known peptides encoded in the human genome, with each being a distinct gene product with similar structure (Figure 1). The Dendroaspis natriuretic peptide (DNP), is structurally similar to ANP, BNP, and CNP, and possesses comparable biologic properties to other NPs. the NP urodilatin (URO or CDD/ANP 95–126), known as renal ANP among the NPs, proANP31−67 Therapeutics in Cardiovascular Disease is secreted by cells of the distal tubule and collecting duct in the kidney in response to increased blood pressure and blood volume.
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