Effects of conjugated oestrogen and droloxifene on the renin-angiotensin system, blood pressure and renal blood flow in postmenopausal women.
OBJECTIVE
The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women.


METHODS
Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication.


METHODS
Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min).


RESULTS
CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments.


CONCLUSIONS
This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.
Endocrine-Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachussets 02115, USA. eseely@partners.org
Ellen W
EW
Seely
K Bridget
KB
Brosnihan
Xavier
X
Jeunemaitre
Kyoko
K
Okamura
Gordon H
GH
Williams
Norman K
NK
Hollenberg
David M
DM
Herrington
D000368:Aged; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004966:Estrogens, Conjugated (USP); D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C038345:droloxifene; D000804:Angiotensin II; D000803:Angiotensin I