Atrial natriuretic factor: Structure and functional properties

In 1964 Jamieson and Palade [1] published their study on the morphological characterization of specific atrial granules, concluding that atrial muscle fibers “form and store a population of granules presumably secretory in nature.” At that time, it had already been postulated that the atria were involved in extracellular volume regulation [2] and, working along different lines of evidence, some investigators were searching for a putative natriuretic hormone [3]. It is therefore surprising that the presence of atrial secretory granules did not command immediate attention as a possible source of a natriuretic substance. More than 15 years elapsed before De Bold et al [4] reported the decisive experiment showing that the atria of mammals indeed contain a natriuretic factor. In this experiment it was found that intravenous bolus administration of crude atrial but not ventricular extract leads to a brisk natriuresis, diuresis, and kaliuresis of very rapid onset (1 to 2 min) and relatively short duration (10 to 20 min) [4]. The peak sodium excretion reached as much as 30- to 40-fold basal levels, a magnitude of action which immediately situated atrial natriuretic factor (ANF) as the most powerful endogenous natriuretic substance described to date. In addition, in the same study it was found that crude atrial extract decreased blood pressure, the time course of this effect closely following its natriuretic effect. Subsequently, the atrium of several mammals, including humans, were shown to contain the atrial natriuretic factor [5]. Since this discovery, progress on the identification and actions of the ANF has been remarkable. In a short span of 3 years, ANF was identified as a peptide or group of peptides having direct vascular as well as natriuretic effects. These peptides were purified, sequenced and synthesized, and the entire sequence of an ANF precursor was established by modern complementary DNA cloning techniques. Furthermore, the effects of pure and synthetic atrial peptides on renal function, smooth muscle contractility, and the renin-angiotensin-aldosterone system have been characterized in broad terms. The present non-inclusive short review is intended as a critical appraisal of the pertinent literature on the chemical and functional properties of ANF with special emphasis on the latter. Some of the open questions and future perspectives will also be considered. An opening cautionary note is pertinent. Until there is direct and unequivocal evidence th