Evidence for a Humoral Natriuretic Factor released by Blood Volume Expansion

Abstract

FOLLOWING the demonstration that diuresis and natriuresis, caused by blood volume expansion with iso-oncotic infusions in dogs, are similar in denervated and innervated kidneys¹, it was logical to attempt the direct demonstration by crossed perfusion of a humoral effector mechanism. This undertaking was preceded by the report of Mills et al.² that diuresis and natriuresis produced by iso-oncotic infusions in dogs could not be prevented by pitressin and mineralocorticoid administration. In the description by de Wardener et al.³ of complicated cross-perfused whole-animal preparations, as well as of isolated kidney perfusions, evidence was advanced for the operation of a natriuretic material following large saline infusions in dogs. Cort and Lichardus⁴, using carotid occlusion in the cat, have shown that a resulting natriuresis, presumed to be due to blood volume redistribution, could be elicited in a second cat by transferred blood. This experiment offered direct evidence of a natriuretic substance by a bioassay procedure in which the stimulus itself could not have influenced the test animal. A large amount of early work led Homer Smith⁵ to deduce the existence of a natriuretic system other than the mineralocorticoid mechanism for regulation of sodium metabolism. Recently, evidence has been accumulating, in particular from the work of Levinsky, Hector and Berliner et al.^6–8, that expansion of the extracellular fluid volume with saline can decrease renal tubular sodium reabsorption in circumstances where neither change in mineralocorticoid levels nor in glomerular filtration rate can explain the effect.