The N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of the atrial natriuretic factor prohormone each circulate in humans and increase in congestive heart failure.

Abstract

Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminus of the prohormone of atrial natriuretic factor (pro-ANF) that have vasodilatory and natriuretic properties were investigated to determine if they circulate in humans. Specific and sensitive radioimmunoassays were developed to amino acids 1-30, 31-67, and 99-126 of pro-ANF. Evaluation of human plasma that had been subjected to reverse-phase high-pressure liquid chromatography suggested that pro-ANFs 1-30 and 31-67 as well as ANF were distinct peaks in human plasma corresponding exactly to pure synthetic peaks of these peptides on high-pressure liquid chromatography. Molecular weight determination of the endogenous immunoreactive peptides measured in plasma by G-50 Sephadex gel permeation chromatography revealed that the pro-ANF 1-30 radioimmunoassay recognized a peptide of 10,000 MW, which is consistent with it measuring the whole N-terminus of pro-ANF (amino acids 1-98) but without ANF (C-terminus) attached to it. The pro-ANF 31-67 radioimmunoassay recognized mainly (more than 95%) a peptide of 3,900-4,000 MW, which corresponds closely with its actual molecular weight of 3,878. Our ANF radioimmunoassay recognizes a peptide in plasma of 3,000 MW with the known molecular weight of ANF being 3,081. The mean circulating concentrations of immunoreactive pro-ANF 1-98, pro-ANF 31-67, and ANF in 54 control subjects were 531±25, 371±+18, and 22±1 fmol/ml (±SEM), respectively. Thirty patients with varying severity of congestive heart failure were also studied. The N-terminus, C-terminus, and pro-ANF 31-67 increased: twofold for New York Heart Association functional Class II, threefold to ninefold for Class III, and 10-to 20-fold for Class IV patients with congestive heart failure. Thus, the N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of pro-ANF as well as ANF circulate normally and increase proportionately to the increasing severity of congestive heart failure. However, because the pro-ANF 31-67 radioimmunoassay was the only assay that discriminated between patients with Class I congestive heart failure and control subjects, this assay may be the most useful to accurately classify the severity of congestive heart failure.

Atrial Natriuretic Peptide Prohormone Gene Expression: Hormones and Diseases That Upregulate its Expression

“…2). These four peptide hormones circulate as distinct peptides after being proteolytically cleaved from their prohormone (24,25) with their biologic effects outlined in Fig. 1.…”

Breed Differences in Natriuretic Peptides in Healthy Dogs

“…NT‐proANP is further cleaved into 3 segments; proANP 1‐30, 31‐67, and 68‐98 24. All segments can be analyzed,3, 4, 6, 8, 17, 18, 25 but the N‐terminal segments have been found to have longer half‐lives and may, therefore, be better suited as diagnostic tools 11, 26, 27, 28, 29.…”

Vessel Dilator Enhances Sodium and Water Excretion and Has Beneficial Hemodynamic Effects in Persons With Congestive Heart Failure

“…1 In congestive heart failure (CHF), vessel dilator increases in the circulation in direct proportion to the amount of sodium and water retention, with persons with more severe CHF having significantly (PϽ0.001) higher circulating concentrations than persons with mild CHF. 3,4 This increase in vessel dilator in the circulation is an apparent adaptive response by vessel dilator to overcome the sodium and water retention that characterizes CHF. [3][4][5][6] The present investigation was designed to determine whether vessel dilator has beneficial diuretic and natriuretic effects in humans with CHF.…”

“…3,4 This increase in vessel dilator in the circulation is an apparent adaptive response by vessel dilator to overcome the sodium and water retention that characterizes CHF. [3][4][5][6] The present investigation was designed to determine whether vessel dilator has beneficial diuretic and natriuretic effects in humans with CHF. Evaluation of whether vessel dilator has beneficial hemodynamic effects on systemic vascular resistance, pulmonary vascular resistance, pulmonary capillary wedge pressure, central venous pressure, pulmonary artery pressure, cardiac output, stroke volume index, mean arterial pressure, and heart rate in CHF subjects was also performed.…”