(Hypertension. 1999;33:323-328.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Estrogen Regulation of Angiotensin-Converting Enzyme mRNA
From The Hypertension and Vascular Disease Center, Division of Surgical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC.
Correspondence to Patricia E. Gallagher, The Hypertension and Vascular Disease Center, Medical Center Blvd, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032. E-mail pgallagh{at}wfubmc.edu
Abstract—Estrogen replacement
therapy is cardioprotective in postmenopausal women; however, the
precise molecular mechanisms for this modulation are not fully
elucidated. We previously showed that chronic estrogen replacement
therapy reduced angiotensin-converting enzyme (ACE)
activity in tissue extracts and serum with an associated reduction in
plasma angiotensin II. A reverse transcriptase–polymerase
chain reaction assay was developed to determine whether estrogen
treatment regulates tissue ACE mRNA concentration. Total RNA was
isolated from kidney cortex, kidney medulla, lung, and aorta of
ovariectomized Sprague-Dawley rats after 21 days of chronic
17ß-estradiol replacement therapy (5 mg pellet per rat SC) or
placebo. A marked decrease in densitometric intensity ratios of
amplified ACE cDNA to elongation factor-1
control cDNA was observed
in all tissues from placebo-treated rats compared with the
estradiol-treated rats (renal cortex: 0.29±0.04 versus 0.14±0.02;
renal medulla: 0.37±0.04 versus 0.24±0.03; lung: 4.49±0.37 versus
2.49±0.59; and aorta: 0.41±0.04 versus 0.29±0.02; all
P<0.05). A comparable reduction in ACE activity was
detected in tissue extracts from kidney cortex, kidney medulla, and
lung of hormone-treated animals. Incubation of purified rat lung ACE
with 1 or 10 µmol/L 17ß-estradiol had no effect on enzyme
activity. These results suggest that estrogen treatment regulates
tissue ACE activity by reducing ACE mRNA concentrations. Thus, the
beneficial cardiovascular effects of estrogen may be
mediated in part by downregulation of ACE with a consequent reduction
in the circulating levels of the vasoconstrictor
angiotensin II, a decrease in the metabolism of
the vasodilator bradykinin, and an increase in the production
of the vasorelaxant angiotensin-(1–7).
Key Words: angiotensin-converting enzyme • estrogen • gene regulation • hormone replacement • reverse transcriptase–polymerase chain reaction
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