Past and Current Perspectives on the Natriuretic Peptides

It is now some 15 years since de Bold and colleagues observed the profound hypotension, diuresis, and natriuresis that occurred following injection of acid extracts of cardiac atria into anesthetized rats (1). As is now well documented, these effects were due to a peptide hormone, atrial natri-ureti...

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Veröffentlicht in:Experimental biology and medicine (Maywood, N.J.) N.J.), 1996-11, Vol.213 (2), p.98-104
1. Verfasser: Flynn, T. Geoffrey
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Sprache:eng
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Zusammenfassung:It is now some 15 years since de Bold and colleagues observed the profound hypotension, diuresis, and natriuresis that occurred following injection of acid extracts of cardiac atria into anesthetized rats (1). As is now well documented, these effects were due to a peptide hormone, atrial natri-uretic factor or peptide (ANF or ANP), which is stored in precursor form in atrial specific granules (for review of discovery and early research on ANP see Ref. 2). ANP is a 28-amino acid disulfide bonded peptide that forms the C terminus of a larger precursor, pro-ANP, and which is released into the circulation in response to local wall stretch induced by increased intraatrial volume (3). Following the initial experiments of Sonnenberg and de Bold (l), several atrial natriuretic peptides were purified, sequenced, and chemically synthesized. Administration of pharmacological doses of synthetic ANP confirmed that the peptide was a potent natriuretic substance with mild hypotensive effects (4-7). Infusion of pharmacological amounts of ANP to a variety of species showed that the peptide evoked a fall in blood pressure that was sustained for a short period of time and a diuresis and natriuresis that was profound but short. Accompanying these changes was an efflux of chloride and potassium, and a fall in the hematocrit. These changes, although the result of large doses of ANP, suggested that release of ANP from the heart might be involved in the control of blood pressure and body volume. Determination of the amino acid sequence of ANP allowed the cloning and sequencing of first the cDNA (8-10) and then the gene for ANP (10, 18). From such studies, it was clear that ANP is synthesized as a precursor, pro-ANP, of 149 to 153 amino acids depending on the species. Cleavage of the hydrophobic signal peptide and in some species of two C-terminal arginines from the precursor produces the 126-amino acid pro-ANP (1-126). The mature and circulating form of the peptide, ANP(99-126) is derived from the C-terminal 28-amino acids and is formed upon exocytosis of the atrial myocyte (19). The presence of a disulfide bond linking the two cysteine residues (Fig. 1) is essential for biological activity (20).
ISSN:0037-9727
1535-3702
1535-3699
DOI:10.3181/00379727-213-44041