Structure, Expression, and Function of Atrial Natriuretic Factor in Extraatrial Tissues*

Abstract

I. Introduction THE MAINTENANCE of water and salt balance in the continuously changing conditions of external and internal environment is one of the most important body functions. This function is maintained by the complex interplay of several neuronal and hormonal systems such as renin-angiotensin-aldosterone, vasopressin, and a recently discovered cardiac hormone. Indeed, cardiac myocytes synthesize and secrete into the blood stream (1) a biologically potent peptide, atrial natriuretic factor (ANF), whose existence was first discovered by de Bold and co-workers in 1981 (2). ANF in a 28 amino acid (AA) peptide (ANF-99-126)¹ which is present at the carboxyl end of a larger precursor molecule [(ANF 1-126; (3)]. The peptide has been found and characterized in the heart of several mammalians (including human, rat, rabbit, bovine, etc.) birds and amphibians (4) and complementary DNA (cDNA) and genomic clones encoding the ANF precursor have been obtained from several species (5). The ANF sequence is highly conserved among all these species suggesting an important physiological role for this new hormone. ANF is thought to contribute to the regulation of extracellular fluid volume and electrolyte balance by increasing the secretion of water and salt via a direct action on the kidney. ANF also produces vasorelaxation of blood vessels and a decrease in cardiac output, and as a consequence of these properties lowers blood pressure and maintains cardiovascular homeostasis. All these actions are mediated by specific high affinity receptors (6, 7) which are present on target tissues where they are coupled to a particulate guanylate cyclase (8).