Further Studies of a Natriuretic Substance Occurring in Human Urine and Plasma

Abstract
Studies are presented which provide additional physiological and biochemical characterization of a natriuretic agent which has been identified in extracts of plasma and urine of human subjects. The natriuretic activity of active fractions was consistently demonstrable in normal hydropenic rats as well as in rats with congenital diabetes insipidus. The induced natriuresis usually developed slowly and could last for several hours. The natriuresis was not usually associated with increases in water or potassium excretion. It occurred without measurable changes in glomerular filtration rate or arterial blood pressure. Altogether, these results suggest that the substance acts to depress sodium reabsorption in the distal tubule. In bioassays of similarly prepared fractions utilizing direct perfusion of the renal artery, an immediate and transient natriuresis has been consistently observed. This immediate response appears to be produced by a substance different from that responsible for the delayed and more prolonged natriuresis, because the immediate response was always associated with a rise in blood pressure in the assay animal. Also, the activity of the agent responsible for the immediate natriuresis did not fluctuate with changes in sodium balance in the experimental subjects. Contamination with this substance may explain the occasional immediate response observed in earlier assays. This experience points to the importance of monitoring blood pressure during assays for natriuretic agents. Additional fractionation studies continue to suggest that the substance occurring in salt-loaded human subjects which causes the more delayed and prolonged natriuresis in assay animals appears to be of a molecular weight of from 10,000 to 50,000.

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