M. Sanada et al., Estrogen replacement therapy in postmenopausal women augments reactive hyperemia in the forearm by reducing angiotensin converting enzyme activity, ATHEROSCLER, 158(2), 2001, pp. 391-397
Citations number
44
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
The precise mechanism of the vasoprotective effect of estrogen replacement
therapy in postmenopausal women is not fully understood. The present study
sought to determine the role of nitric oxide (NO) and angiotensin-convertin
g enzyme (ACE) in the vasodilator response of the forearm vessels induced b
y estrogen administration to postmenopausal women. Subjects were divided in
to two groups. One group received conjugated equine estrogen (0.625 mg dail
y) orally for 3 months (n = 26), while the other received no treatment (con
trol group, n = 10). Forearm blood flow was measured by strain-gauge plethy
smography. The concentrations of nitrite/nitrate (metabolites of NO), ACE a
ctivity, and lipid parameters were measured. Basal forearm blood flow, body
weight, blood pressure, and heart rate were similar at baseline in both gr
oups. After 3 months of estrogen administration, the maximal forearm blood
flow response during reactive hyperemia and the serum level of nitrite/nitr
ate each showed a significant increase over baseline values: from 23.6 +/-
2.0 to 36.5 +/- 3.1 ml/min per 100 ml tissue (P < 0.01), and from 24.8 +/-
2.3 to 38.6 +/- 3.6 <mu>mol/l (P < 0.01), respectively. Plasma levels of AC
E activity were significantly reduced from baseline after 3 months of estro
gen treatment (from 12.2 +/- 0.6 to 10.9 +/- 0.6 IU/l, P < 0.01). No change
s were seen in controls. The change in forearm blood flow after sublingual
nitroglycerin was similar at baseline versus after 3 months of estrogen adm
inistration. The increase in the serum level of nitrite/nitrate after 3 mon
ths of estrogen therapy showed a significant inverse correlation (r = 0.52,
P < 0.01) with the reduction in the plasma level of ACE activity. There wa
s no significant correlation between the increase in serum nitrite/nitrate
and any change in serum lipids, blood pressure, or other parameters. The ad
ministration of oral estrogen to postmenopausal women for 3 months increase
d the NO-mediated forearm endothelium-dependent vasodilatation. This was li
kely due, at least in part, to ACE inhibition. The latter may be one mechan
ism by which ERT provides its well-known cardiovascular benefit. (C) 2001 E
lsevier Science Ireland Ltd. All rights reserved.