Effect of ethinyl estradiol on renin activity and on the concentrations of renin substrate and aldosterone in plasma of ovariectomized women

Abstract

The effect of high doses of ethinyl estradiol (0.4 mg/day) on renin substrate concentration, renin activity and aldosterone concentration in plasma was studied in eight ovariectomized women. Plasma renin substrate (angiotensinogen) increased already within 24--48 h, reaching a maximum on the third to fifth day after starting estrogen treatment. Thereafter, renin substrate concentration remained relatively constant in a range which was fourfold above the baseline levels. The increase of plasma renin activity was less pronounced and showed considerable between-patient variability; this increase was statistically significant only after 48 hours of estrogen intake. A rise in plasma aldosterone concentration was observed in two of four subjects examined. In one patient treated with 5 mg estradiol benzoate intramuscularly, plasma renin activity increased without any measurable change in renin substrate concentration. Only in one subject treated with ethinyl estradiol did plasma renin activity increase before plasma renin substrate concentration; the results presented do not preclude factors other than the stimulation of renin substrate synthesis in the liver from contributing to the activation of the renin-aldosterone axis during treatment with ethinyl estradiol.

Chronic Estradiol Treatment Decreases Angiotensin II Receptor Density in the Anterior Pituitary Gland and Adrenal Cortex but Not in the Mesenteric Artery

“…This finding is in agreement with Menard and Call [28] who have shown that estradiol treatment in rats produced a rapid increase within 6 h of plasma renin substrate and that following a transient 48-hour increase, plasma renin activity fell slightly below normal levels by day 6 when plasma renin concentrations were reduced by half. Although conflicting results have been published [for review see 33], it can be generally con cluded that in man, estrogens increase circulating All [5] and plasma renin activity [22,23]. These values approach normal levels with chronic treatment as plasma renin con centrations are being suppressed [23, 27, 28.…”

Estrogen Modulates AT 1 Receptor Gene Expression In Vitro and In Vivo

“…In this context, enhanced production of angiotensinogen 10,11 and reduced levels of ACE 13,23 have been observed, whereas the effect of estrogens on renin are the subject of ongoing controversy. 10,13,23 In ovariectomized rats, estrogen deficiency causes vascular overexpression of the AT 1 receptor. In this short-term model, the blood pressure is not elevated significantly, probably because of the compensatory decrease of circulating renin levels.…”

Protektion des kardiovaskulären Systems durch Östrogene - Die Rolle des Renin-Angiotensin-Systems -

“…Unter Östrogenersatztherapie kommt es zu Interaktionen mit dem Renin-Angiotensin-System (18,19,20,21). Es konnte gezeigt werden, dass die Serumspiegel von Angiotensinogen erhöht, die von Angiotensin-Converting-Enzyme (ACE) vermindert sind.…”