Synthesis of atrial natriuretic polypeptide in human failing hearts. Evidence for altered processing of atrial natriuretic polypeptide precursor and augmented synthesis of beta-human ANP.

Abstract

To elucidate the synthesis of atrial natriuretic polypeptide (ANP) in the failing heart, 20 human right auricles obtained at cardiovascular surgery were studied. The concentration of ahuman ANP-like immunoreactivity (a-hANP-LI) in human right auricles ranged from 13.8 to 593.5 Ag/g, and the tissue a-hANP-LI concentration in severe congestive heart failure (CHF) (New York Heart Association [NYHAI functional class III and class IV) (235.4±57.2 gg/g) was much higher than that in mild CHF (NYHA class I and class II) (52. 5±15.6 Ag/g). Atrial a-hANP-LI levels were significantly correlated with plasma concentrations of a-hANP-LI in these patients (r = 0.84, P < 0.01).High performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for ANP revealed that the a-hANP-LI in the human auricle consisted of three major components of ANP, v-human ANP ('y-hANP), 6%human ANP (8-hANP) and a-human ANP (a-hANP). Comparing percentages of 'yhANP, fl-hANP, and a-hANP in a-hANP-LI in severe CHF with those in mild CHF, the predominant component of ahANP-LI was y-hANP in mild CHF, whereas 8-hANP and/or a-hANP were prevailing in severe CHF and, especially, 8-hANP was markedly increased in human failing hearts.These results demonstrate that the total ANP concentration in the atrium of the human heart is increased in severe CHF and that the increase of ANP in the human failing heart is mainly due to the increase of small molecular weight forms of ANP,,j-hANP, and a-hANP, especially ,8-hANP, and indicate that the processing of ANP precursor, or 'y-hANP, in the human failing heart differs from that in the normal heart, suggesting that the failing heart augments synthesis and secretion of ANP as one of its own compensatory responses.

Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene.

“…All DNA sequences were determined using the dideoxy chain-termination method (23) (3). The antiserum (M-7) could be used at a final 1:10,000 dilution.…”

“…One of these factors, atrial natriuretic peptide (ANP),' is synthesized in and secreted from the heart, and acts as a cardiac hormone with a variety ofbiological actions including natriuresis, diuresis, vasorelaxation, and inhibition ofrenin and aldosterone secretion ( 1,2). ANP is found at the highest concentration in the atrium, and the circulating ANP is mainly derived from the atrium (1)(2)(3). Although the ANP gene expression in the ventricle is -100-fold lower than in the atrium, ventricular expression is up-regulated in patients with congestive heart failure (CHF) and animal models ofventricular hypertrophy (4)(5)(6).…”

Plasma brain natriuretic peptide — an independent predictor of cardiovascular mortality in acute heart failure

“…In the normal situation human ANP is synthesized mainly in the atrium and gene and protein expression increases in the atriocytes in heart failure [3]. There is also evidence that ANP is also produced in the ventricle in disease states [4].…”

Natriuretic Peptide Receptor Guanylyl Cyclase-A Protects Podocytes from Aldosterone-Induced Glomerular Injury

“…14 ANP and BNP are secreted predominantly by the cardiac atrium and ventricle, respectively, upon cardiac overload. [14][15][16] They exert various biologic effects by acting on guanylyl cyclase-A (GC-A)/natriuretic peptide receptor-A (NPR-A), which is the major and possibly the only receptor for ANP and BNP, through the activation of cGMP/ cGMP-dependent protein kinase. 17 GC-A is abundantly expressed in blood vessels and the heart 17 ; within the kidney, it is localized in glomeruli, thin limbs of Henle's loop, cortical collecting ducts, and inner medullary collecting ducts.…”