Hormone replacement therapy increases plasma level of angiotensin II in postmenopausal hypertensive women.

The renin-angiotensin-aldosterone system plays a major role in the pathogenesis of hypertension by enhancing the production or the activity of angiotensin II (ANG II). We evaluated the effects of hormone replacement therapy (HRT) on the renin-angiotensin-aldosterone system and on bradykinin in postmenopausal women (PMW) who were hypertensive or normotensive. Subjects included 28 PMW whose elevated blood pressure (BP) was well controlled on antihypertensive agents excluding diuretics, angiotensin-converting enzyme (ACE) inhibitors, and ANG II receptor antagonists. As controls, we evaluated 16 normotensive PMW. All subjects received oral HRT daily for 6 months. The plasma levels of angiotensin I (ANG I), ANG II, and bradykinin as well as plasma renin activity (PRA) showed a significant increase in HRT in the hypertensive group, but not in the normotensive group. The serum ACE activity showed a significant decrease in both groups, but the plasma level of aldosterone was unchanged. Despite the decrease in serum ACE activity, there was an increase in the plasma ANG II level. Hormone replacement therapy increased the level of ANG II in the hypertensive women, but their BP was unaffected. The increase in plasma bradykinin level may maintain homeostasis in the presence of an increase in plasma ANG II, which is a risk factor for cardiovascular disease. Hormone replacement therapy was associated with a decrease in serum ACE and an increase in plasma bradykinin in hypertensive PMW. Accordingly, the protective effect of HRT against cardiovascular disease in PMW can be provided by a decrease in ACE activity and an increase in bradykinin.