PubMed1990
Although ANF research started 30 years ago, the atrial natriuretic factor (ANF) was only discovered recently (1981). The presence of such a factor has been suspected for many years because of histological and physiological arguments. In 1956, Kish found "dense granules" in the atrial walls of guinea pigs. Gauer and Henry could explain some of their experimental results on diuresis and natriuresis only by suggesting the presence of a third hormonal factor, but neither by the renin-angiotensin system, nor the anti-diuretic hormone. Hall et al. were the first to recognize a link between the granules and water and sodium metabolism. But it was De Bold who published the crucial experiment in 1981: injecting right atrial extracts to anaesthetized rats rapidly induced intense and transitory diuresis and natriuresis. ANF was born, and, at the same time, the concept of the heart as an endocrine gland. Indeed, ANF corresponds to the strict definition of a hormone. It has the following properties: natriuresis and diuresis via an increase in glomerular filtration fraction without any major changes in renal plasma flow; direct vasodilation of the large arteries with only few effects on small arterioles and veins. The stimuli for ANF secretion are mechanical and pharmacological, especially drugs currently used by anaesthetists. Atrial distension is the main mechanical stimulus. An increase in atrial transmural pressure is always followed by a release in ANF, but this effect is not constant for increases in intra-luminal pressure. It is the former pressure gradient alone that reflects the volume of the right atrium, the mechanical stimulus for ANF secretion. Tachycardia, or, more precisely, an increase in the atrial contraction rate, also leads to an important release of ANF. Cardiac nerves are not necessary for this, as demonstrated by studies in heart transplant patients. Only few pharmacological agents have been shown to really stimulate ANF secretion. In rats, morphine has a direct secretory effect, whereas ketamine hydrochloride, diethylether and chloral hydrate do so by increasing the release of catecholamines. The effects of alpha, beta adrenergic agonists and calcium agonists remain controversial. ANF, which has diuretic and vasodilator effects, plays a part, together with the renin-angiotensin system and the anti-diuretic hormone, in blood volume control in mammals. However, it has a special role to play, because it is a rapid release hormone: rapid vascular filling leads to an increase in ANF in less than 1 minute, with a parallel increase in diuresis.