Effects of heparin treatments in vivo and in vitro on adrenal angiotensin II receptors and angiotensin II-induced aldosterone production in rats

Abstract

To evaluate the heparin effects in vivo and in vitro on adrenal angiotensin II receptors and angiotensin II-induced aldosterone production, we examined the angiotensin II binding and the maximum angiotensin II-induced aldosterone production using adrenal glomerulosa cells from rats treated with a heparin preparation containing benzyl alcohol (1500 IU/kg, twice daily for 6 weeks) or cells to which heparin (300 IU/l) was directly added. Comparison was made using the cells from rats treated with vehicle or the cells to which vehicle was directly added. Specific binding of [125I]iodo-angiotensin II was decreased in the cells from heparin-treated rats or in the heparin-treated cells. Scatchard analysis showed that the decrease in binding was due to a decrease in both the number and the affinity of angiotensin II receptors in the cells from heparin-treated rats and a decrease in the number, but not the affinity, of the receptors in the heparin-treated cells. Heparin also caused a decrease in the maximum angiotensin Il-induced production, but not the basal production, of aldosterone in the cells from hepari n\x=req-\ treated rats and in the heparin-treated cells. These data suggest that heparin interacts with adrenal angiotensin II receptors to inhibit the angiotensin Il-induced aldosterone production.

A low molecular weight heparin decreases plasma aldosterone in patients with primary hyperaldosteronism

“…The mechanism of this effect of heparinoids on aldosterone is not known. Presumably it is due to a direct action on aldosterone synthesis, although a decrease in aldosterone production due to a decrease in the sensitivity to angiotensin II has also been suggested [6][7][8]. In the present cases, there cannot have been an effect on renin or on the sensitivity to renin, since renin was so low as to be more or less undetectable, and, if anything, it tended to increase during treatment.…”

Heparin-Induced Hyperkalemia in an Extremely-Low-Birth-Weight Infant: A Case Report

“…Heparin lowers the number and affinity of angiotensin II receptors in the adrenal zona glomerulosa, which results in decreased plasma and urinary aldosterone concentrations (2,7). …”

Heparin‐Induced Hyperkalemia in Chronic Hemodialysis Patients: Comparison of Low Molecular Weight and Unfractionated Heparin

“…The features of heparin induced aldosterone suppression and hyperkalemia have been recently reviewed in depth (7). Although the precise mechanisms whereby heparin inhibits aldosterone production has not been definitively established, this inhibitory effect is specific to the zona glomerulosa, and in vitro experiments conducted on rat adrenal cells demonstrated decreased binding of angiotensin II resulting from the reduction in both the number and affinity of angiotensin II receptors (8). The aldosterone inhibitory effect occurs rapidly following the initiation of therapy (sodium loss and potassium retention may be detectable after 1 to 3 days), is maximal after 3 to 5 days, and wanes within 1 to 3 days of discontinuation.…”