Effect of long-term hormone replacement therapy on angiotensin-converting enzyme activity and bradykinin in postmenopausal women with essential hypertension and normotensive postmenopausal women.
OBJECTIVE
Hormone replacement therapy (HRT) reduces the incidence of cardiovascular disease in postmenopausal women. Three-month short-term HRT in postmenopausal women with essential hypertension increased the plasma concentrations ofbradykinin with decreased serum angiotensin-converting enzyme (ACE) activity, which may be partially responsible for the cardioprotective effects of HRT. The objective was to determine whether 12-month long-term HRT in postmenopausal women with essential hypertension would maintain the decreased ACE activity and increased bradykinin levels and whether long-term HRT would increase the plasma bradykinin concentrations of normotensive postmenopausal women who had shown no significant changes in the 3-month HRT study, despite their decreased serum ACE activity.


METHODS
Twenty hypertensive and 15 normotensive postmenopausal women were treated with conjugated estrogens (0.625 mg/day) and medroxyprogesterone (2.5 mg/day) for 12 months. Twenty hypertensive and 15 normotensive postmenopausal women were used as controls. The controls were not treated with HRT. Serum ACE activity and plasma bradykinin concentrations were measured at baseline and at 12 months.


RESULTS
Long-term HRT in both hypertensive and normotensive postmenopausal women significantly decreased serum ACE activity from 15.5+/-0.7 IU/L and 16.0+/-0.9 IU/L, respectively, at baseline to 13.3+/-0.5 IU/L and 14.2+/-0.9 IU/L, respectively, 12 months after the start of HRT (p < 0.05 and p < 0.05, respectively). Long-term HRT in both hypertensive and normotensive postmenopausal women also significantly increased plasma bradykinin concentrations from 22.1+/-4.4 pg/mL and 19.2+/-3.0 pg/mL, respectively, at baseline to 86.7+/-21.2 pg/mL and 73.5+/-23.0 pg/mL, respectively, 12 months after the start of HRT (p < 0.01 and p < 0.05, respectively). No significant changes in serum ACE activity or plasma bradykinin concentrations were observed in the control groups.


CONCLUSIONS
Long-term HRT in hypertensive and normotensive postmenopausal women decreases their serum ACE activity and increases their plasma bradykinin concentrations. Thus, maintenance of elevated bradykinin with decreased serum ACE activity by HRT may be useful in reducing the risk of cardiovascular disease in both hypertensive and normotensive postmenopausal women.
Nogawa
N
N
Cardiovascular Hospital of Central Japan, Gunma.
Sumino
H
H
Ichikawa
S
S
Kumakura
H
H
Takayama
Y
Y
Nakamura
T
T
Kanda
T
T
Mizunuma
H
H
Kurabayashi
M
M
D000284:Administration, Oral; D000368:Aged; D001920:Bradykinin / Q000097:blood*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004334:Drug Administration Schedule; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000517:prevention & control*; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D017698:Postmenopause
D004966:Estrogens, Conjugated (USP); D007703:Peptidyl-Dipeptidase A; D008525:Medroxyprogesterone; D001920:Bradykinin