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A natriuretic and diuretic response to whole blood infusion in the rat, exaggerated and sustained by intravenous reinfusion of excreted urine, was shown to be associated with increased glomerular filtration and reduced tubular reabsorption. Cross-circulation of animals so responding (donor rats) with isovolemic recipients led to a modest natriuretic and diuretic response in the latter, not accounted for by altered physical composition of the blood nor by observed changes in filtration rate or arterial blood pressure. The recipient natriuresis was unchanged when nephrectomized donors were used and it occurred in experiments in which donor urine was simultaneously replaced by intravenously infused Ringer-Locke solution; the natriuretic property of the cross-circulating blood could therefore not have been due to reinfusion of urinary constituents, nor to accumulation of metabolites, nor to a factor of renal origin. A recipient natriuresis was also observed when the expanded and urine reinfused donor had been acutely adrenalectomized, ruling out an altered secretion of adrenal cortical or medullary hormones as a principal cause of this natriuresis; the data, however, do not exclude participation of reduced aldosterone secretion in the normal effector mechanism. In control experiments in which whole blood was exchanged for donor blood, a small delayed natriuresis did occur in the recipient; this could be completely prevented by administration of aldosterone. In similar exchange experiments with adrenalectomized donors, a small natriuresis developed in the recipient before blood administration but declined afterwards. These minor natriuretic effects probably resulted from altered mineralocorticoid content of the cross-circulating blood due to factors other than blood volume change. The larger natriuretic response seen in all recipients when the donor was volume expanded must have been due largely to a humoral natriuretic factor of other than renal or adrenal origin.

A Humoral Component of the Natriuretic Mechanism in Sustained Blood Volume Expansion