The Natriuretic and Aldosterone-Suppressive Action of Heparin and Some Related Polysulfated Polysaccharides1

Abstract

In order to extend earlier observations on the natriuretic effect of heparinoids in man, the effect of several sulfated polysaccharides on urinary sodium and potassium excretion was studied in dogs receiving low sodium diets. In patients, the effect of heparinoids, not tested before, on the excretion of sodium, potassium, creatinine and aldosterone was studied to extend previous observations in man. The pattern of sodium excretion observed in dogs during treatment with certain heparinoids differs from that seen in man in that natriuresis starts on the first day of drug administration. As in man, the enhanced sodium output continues for several days after injections of the drug are terminated. As in earlier studies, it was observed that urinary aldosterone excretion in man during natriuresis induced by the heparinoid, Rol-8307 (N-formyl-chitosan polysulfuric acid), fell to very low levels. The same result was obtained with SP 54 (xylan polysulfuric acid). On the contrary, chondroitin sulfate A showed only a slight and indefinite fall in urinary aldosterone excretion. From a survey of the results obtained with 4 heparinoids indogs and 6 polysulfated polysaccharides in man, the tentative conclusion is reached that a relatively high sulfate content of the drugs is necessary for a natriuretic effect to occur. Although the mechanism by which heparin and related polysaccharides cause natriuresis and elicit a fall of urinary aldosterone excretion is not known, some facts from the literature suggest that these compounds may interfere with the renin-angiotensin system.