Therapeutic usefulness of Ca blocking effect of atrial natriuretic factor

pp 263-271

Abstract

Atrial natriuretic factor is a hormone produced mainly by atrial myocytes, whose physiological role described up to date consist in natriuresis and diuresis increase, renin-aldosterone secretion inhibition, vasopressin inhibition, and the ability to shift fluid from the intra-vascular to the extravascular compartment. We observed that atrial natriuretic factor modulates sympathetic neurotransmission, at presynaptic level and at chromaffin cells, increasing the uptake and reducing norepinephrine synthesis, release and turnover. The present study was designed to investigate atrial natriuretic factor effects on the calcium dependent mechanism involved in the catecholamine release process. We demonstrated that this factor acts as a partial inhibitor of calcium channels, showing an additive effect with verapamil, nifedipine, and diltiazem. The atrial natriuretic factor decreased spontaneous and induced release of hypothalamus norepinephrine and adrenal catecholamines. Different aspects of the biological activity of atrial natriuretic factor suggest a posible role as a natural antihypertensive substance. It has potentially benefitial inhibitory effects on the renin-aldosterone system and the interference with the sympathetic drive. However, the very short half-life of this factor and the fact that it can only be given intra-venously limits its therapeutic use. The recent introduction of inhibitors of neutral endopeptidase, the enzyme that degrades atrial natriuretic factor promises very exciting therapeutic possibilities.