Effects of estradiol and the angiotensin II receptor blocker irbesartan on vascular function in postmenopausal women.
OBJECTIVE
Estradiol and angiotensin receptor blockers have prominent effects on the renin-angiotensin-aldosterone system. The purpose of this study was to determine whether irbesartan, an angiotensin receptor blocker, has a greater effect on vascular function when combined with estradiol, compared with irbesartan alone, in hypertensive postmenopausal women.


METHODS
Fifty-one women were studied while off any antihypertensive medications or hormone therapy at baseline and after randomization to one of four treatment arms for 12 weeks: (1) irbesartan and estradiol, (2) irbesartan and placebo, (3) estradiol and placebo, and (4) placebo/placebo. Estradiol and placebo arms served as control groups. Blood pressure, brachial reactivity, aldosterone, insulin, glucose, 24-hour urinary catecholamines, urinary sodium, and creatinine were measured. Fisher's exact test was used for comparison of differences in blood pressure in the treatment arms. Paired t test and analysis of variance were also performed for within- and between-group analysis.


RESULTS
A significantly larger number of women in the irbesartan and estradiol group had a decrease of 5 mm Hg or more in both systolic and diastolic blood pressures (P < 0.05) compared with irbesartan alone group. Forearm vascular reactivity was increased significantly compared with baseline (P < 0.05), and there was a significant decrease in the serum aldosterone level after treatment compared with baseline (P < 0.05) in the irbesartan and estradiol combination group. Fasting glucose and insulin, urinary sodium/creatinine ratio, and catecholamines were similar at each time point.


CONCLUSIONS
The results suggest that irbesartan and estradiol, when used in combination, may cause a greater lowering of blood pressure in postmenopausal hypertensive women. This effect may be mediated via increased vasodilation and lower aldosterone levels. These results warrant further testing in larger clinical trials.
Mirza
Faryal S
FS
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Ong
Paul
P
Collins
Peter
P
Okamura
Kyoko
K
Gerhard-Herman
Marie
M
Williams
Gordon H
GH
Seely
Ellen W
EW
D000368:Aged; D000450:Aldosterone / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000652:urine; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D000077405:Irbesartan; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D016387:Women's Health
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D013777:Tetrazoles; D000450:Aldosterone; D004958:Estradiol; D012964:Sodium; D003404:Creatinine; D000077405:Irbesartan