Atrial natriuretic factor. Is it physiologically important?

T he heart as an endocrine gland was unequivocally established with the ingenious experiments of DeBold and coworkers 1981 that demonstrated the existence of atrial natriuretic factor (ANF).1 These and subsequent studies have reported that ANF exists as a prepro-ANF molecule that is stored as a 126-amino-acid pro-ANF within atrial granules.2,3 In response to atrial stretch, pro-ANF is cleaved by a membrane-bound protease and released into the circulation as a 28-amino-acid peptide.4,5 Although hundreds of studies on ANF appear annually, the functional role of ANF in physiological regulation remains unclear. Based on studies that use exogenous administration of synthetic ANF, it is clear that pharmacological concentrations of ANF may decrease cardiac filling pressures and arterial pressure, increase sodium excretion, and inhibit activation of the renin-angiotensin-aldosterone system.6,7 Despite such pharmacological actions, the role of ANF in the physiological regulation of the circulation remains controversial.