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

Abstract

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.

Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women

“…As observed in a prior study of hypertensive women, 29 CEE significantly increased circulating Ang II concentrations consistent with a stimulatory effect of estrogen on angiotensinogen synthesis. 30 As reported previously, ACE inhibition significantly increased PRA without altering either Ang II or aldosterone concentrations, consistent with decreased conversion of tissue Ang I to Ang II, a loss of feedback inhibition of renin synthesis by Ang II, and subsequent "escape" of circulating Ang II and aldosterone concentrations.…”

Attenuated Responses to Angiotensin II in Follitropin Receptor Knockout Mice, a Model of Menopause-Associated Hypertension

“…27 In addition, Ang II has been implicated in hypertension associated with estrogen deficiency. 6,[27][28][29] Furthermore, 27-29 estrogen attenuates Ang II-mediated actions. 6,30 To investigate whether Ang II effects are upregulated in FORKO mice, we assessed contractile responses of small mesenteric arteries to increasing concentrations of Ang II.…”

Effects of Hormone Replacement Therapy on Left Ventricular Hypertrophy and Growth-Promoting Factors in Hypertensive Postmenopausal Women

“…One proposed mechanism is that the regression of LVH as a result of HRT may be due to the direct suppressive effects of estrogen on both cardiac myocytes and fibroblasts, since ER α and ER β have been detected in both cardiac myocytes and fibroblasts (36). The other is that the regression of LVH may be due to an indirect effect of estrogen on cardiomyocytes mediated by systemic growth-promoting factors, such as endothelin-1, catecholamine, and angiotensin II, since recent studies have reported that HRT affects endothelin-1 (37), catecholamine (38), and angiotensin II (39).…”