Increased Release of the N-Terminal and C-Terminal Portions of the Prohormone of Atrial Natriuretic Factor During Immersion-Induced Central Hypervolemia in Normal Humans

Abstract

Absfracf. The role of peptides from the N terminus and C terminus of the 126 amino acid atrial natriuretic factor (ANF) prohormone in modulating renal sodium and water handling has not been defined. Since water immersion to the neck (NI) provides an acute central volume expansion identical to that produced by 2 liters of saline but without plasma compositional change, immersion to the neck was used to assess the N-terminal and C-terminal portions of the ANF prohormone response to acute central blood volume expansion in seven seated sodium-replete normal subjects. Both the C terminus, which contains amino acids 99-126 and is identical to ANF, and the whole N terminus (i.e., amino acids 1-98) increased promptly with NI and peaked after 1 hr of immersion. A M, 3900 peptide from the midportion of the N terminus consistent with amino acids 31-67 (Lea, pro-ANF-31-67) also increased with NI and followed a pattern of increasing circulating concentration nearly identical to that of the whole N terminus of the prohormone, except that its maximal concentration was at the second hour of the 3 hr of NI. With cessation of immersion, ANF decreased to preimmersion levels within 1 hr whereas the N terminus and pro-ANF-31-67, although their circulating concentrations were decreasing, were still significantly elevated at 1 hr. These findings suggest that the increase in plasma ANF, the N terminus of the ANF prohormone, and pro-ANF-31-67 from the midportion of the N terminus, with natriuretic properties similar to ANF, contribute to the natriuretic response to NI, implying a physiologic role for these atrial peptides in modulating volume homeostasis in humans. [P.S.E.B.M. 1989[P.S.E.B.M. , Vol 1921 trial natriuretic factor (ANF), the 28-amino acid C-terminal end of the 126-amino acid ANF A prohormone synthesized in cardiac myocytes, has potent natriuretic, vasodilatory, and renal hemodynamic effects (1-3). Recent evidence indicates that '

Increased Release of Kaliuretic Peptide during Immersion-Induced Central Hypervolemia in Cirrhotic Humans

“…The basal kaliuretic peptide concentrations var ied independently of either systolic or diastolic arterial pressure (table 1). The basal circulating levels of ANF were not significantly different from those of 7 healthy individuals without cirrhosis who underwent a similar immersion study [25] (fig. 3).…”

“…3). The preimmersion circulat ing concentrations of the kaliuretic peptide, however, were significantly higher (p < 0.05) in the cirrhotic sub jects versus those of the healthy subjects [25], as shown in figure 3.…”

“…Previous studies have demonstrated that head-out wa ter immersion is a well-defined volume expansion model that produces a prompt, marked, and sustained central hypervolemia without the necessity of infusing exogenous volume expanders and, thus, without altering the plasma composition [16][17][18][19][20], Water immersion is a readily uti lized experimental model for reproducibly producing a marked and sustained stimulation of release of ANF (C terminus of prohormone) [21][22][23][24] and the N terminus of the ANF prohormone in both healthy and cirrhotic human subjects [25,26], Although kaliuretic peptide has recently been demonstrated to circulate in normal human subjects [13,15], heretofore, there has been no investigation on kaliuretic peptide in cirrhotic subjects. The present study was undertaken to examine time course and magnitude of release of kaliuretic peptide in comparison with ANF (amino acids 99-126 of the prohormone) in cirrhotic human volunteers during acute central volume expansion.…”

Atrial Natriuretic Peptide Increases Urodilatin in the Circulation

“…The lowest detectable concentrations were 40 fmol (140 pg), 35 fmol (136 pg), 5 fmol (15 pg) and 1.4 fmol (4.3 pg)/tube, whereas their nonspecific binding was 2.1, 2.5, 2.7 and 2.8% for long-acting natriuretic peptide, vessel dilator, kaliuretic peptide and ANP RIAs, respectively. Serial dilution of pooled plasma revealed excellent parallelism of standards and unknowns in these assays [12,14,16].…”

“…The present investigation was designed (1) to re-examine with a more sensitive assay whether urodilatin circulates and (2) to determine whether ANP influences the release of urodilatin, utilizing high-performance gel permeation chromatography (HP-GPC) and reverse-phase high-pressure liquid chromatography (HPLC) followed by urodilatin assay of human plasma and urine of humans who received a 1-hour infusion of ANP. As vessel dilator, long-acting natriuretic peptide and kaliuretic peptide from the N-terminus of the ANP prohormone are released simultaneously with ANP with central hypervolemia in vivo [12,31] and from isolated atria in vitro [32] and with rapid heart beats of 125 beats/min or more [33], the effect of these peptides on the release of urodilatin was also incorporated into this investigation. Thus, the effects of ANP, long-acting natriuretic peptide, vessel dilator and kaliuretic peptide on the release of urodilatin were examined by measuring the concentration of urodilatin in plasma and urine before, during, and for 3 h after the infusion of each of these peptides at their 100-ng/kg BW W min concentrations for 60 min.…”