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 in dogs 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. (J. Clin. Endocrinol. & Metab. 24: 35,1964)

The Regulation of Aldosterone Secretion in Anephric Man

“…One additional factor which must be considered is the effect of heparin administration during each of the dialyses. Heparin in doses of 300-400 mg per day has been shown to suppress aldosterone excretion and promote natriuresis and potassium retention (27,28).…”

Pathogenesis of Endocrine Abnormalities in Uremia*

“…This decrease in total body potassium, which is frequently not reflected in its circulating levels, may include decrements in adrenal cortical potassium content, thereby suppressing aldosterone secretion. 3) The repeated heparin administration required for anticoagulation during dialysis might interfere with aldosterone secretion, since this agent is known to possess significant aldosterone inhibitory potential (114).…”

Inhibition of Renin by Heparin1

“…Furthermore, heparin administration has resulted in clearing of edema fluid in congestive cardiac failure or the nephrotic syndrome (2, 3, 21). Schlatmann et al (2) and others (3) showed that the natriuretic and diuretic effects of heparin in congestive heart failure are associated with suppression of aldosterone secretion. There is, therefore, considerable evidence to indicate that heparin can reduce aldosterone secretion.…”

“…(J Clin Endocr 27: 699,1967) H EPARIN is known to inhibit certain enzymes (1). In addition, administration of heparin or of related substances has been shown to reduce aldosterone secretion (2,3). This effect has been thought to result from heparin binding of angiotensin (4), or from heparin interference with renin activity (2).…”

“…In addition, administration of heparin or of related substances has been shown to reduce aldosterone secretion (2,3). This effect has been thought to result from heparin binding of angiotensin (4), or from heparin interference with renin activity (2). However, because heparin and heparinoids reduced aldosterone secretion in primary aldosteronism, two groups (5,6) have suggested that these substances act instead to inhibit directly the adrenal cortical synthesis or release of aldosterone.…”