THE NEUROENDOCRINE CONTROL OF ATRIAL-NATRIURETIC-PEPTIDE RELEASE

In the initial experiments reviewed here, we show that atrial natriure tic peptide (ANP) plays an important inhibitory role in the control of sodium chloride and water intake since injections of ANP into the thi rd ventricle (3V) caused a reduction in dehydration-induced drinking a nd also the drinking of salt in salt-depleted rats. Attention was then turned to the possible role of the brain ANP neurons in producing nat riuresis which had earlier been shown to be caused by stimulations wit hin the anterior ventral third ventricular region (AV3V), Stimulation in this region by carbachol produced natriuresis accompanied by a dram atic increase in plasma ANP concentrations and increased content of th e peptide in medial basal hypothalamus (MBH), neurohypophysis (NH) and anterior pituitary gland (AP), without alterations in the content of ANP in lungs or atria, This suggested that the natriuresis resulting f rom the stimulation is brought about, at least in part, by the release of ANP from the brain, Conversely, there was a dramatic decline in pl asma ANP at both 24 and 128 h after AV3V lesions had been placed, In v iew of the much larger quantities of the peptide stored in the atria, it is probable that the changes in the atrial release of the peptide w ere the main factors altering plasma ANP, but that there was concomita nt alteration in the release of brain ANP as well, Blood volume expans ion (EVE) by intraatrial injection of isotonic saline in the rat is a profound stimulus for ANP release. Lesions in the AV3V region, median eminence, or neurohypophysectomy blocked EVE-induced release of ANP in dicating the crucial participation of the CNS in the response of ANP a nd natriuresis. Baroreceptor impulses from the carotid-aortic sinus re gions and the kidney are important in the neuroendocrine control of AN P release since deafferentation of these regions lowered basal plasma ANP concentrations and prevented the increase after EVE. The evidence indicates that the ANP release, in response to EVE, is mediated by aff erent baroreceptor impulses to the AV3V, which mediates the increased ANP release via activation of the hypothalamic ANP neuronal system, Ou r recent data support the hypothesis that EVE causes the release of AN P from ANPergic neurons in the hypothalamus that in turn stimulates re lease of oxytocin from the neurohypophysis. This oxytocin acts to rele ase ANP from the right atrium that has negative chrono-and inotropic e ffects in the right atrium to reduce cardiac output, thereby reducing effective circulating blood volume, Then, the released ANP circulates to the kidneys and evokes natriuresis to return circulating blood volu me to normal, This is further accomplished by reduction in intake of w ater and salt mediated also by brain ANP.