Cited by 290Renin-Angiotensin System StudiesEstrogen and related hormone effectsEicosanoids and Hypertension Pharmacology

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Estrogen Regulation of Angiotensin-Converting Enzyme mRNA

Gallagher, Patricia E., Li, Ping, Lenhart, John R., Chappell, Mark C., Brosnihan, K. Bridget·1999·Hypertension

DOI 10.1161/01.hyp.33.1.323

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Abstract

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 17β-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-1α 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 17β-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).

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10.1161/circ.89.5.8181150 · DOI
10.1161/atvb.17.6.1128 · DOI
10.1161/hyp.27.3.523 · DOI
10.1161/hyp.29.1.394 · DOI
10.1161/hyp.31.1.362 · DOI
10.1161/atvb.15.7.827 · DOI
10.1161/circ.95.1.39 · DOI

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Authors: Gallagher, P. E., Li, P., Lenhart, J. R., Chappell, M. C., & Brosnihan, K. B.
Affiliations: Wake Forest University Health Sciences (US)
ORCID: Gallagher, Patricia E.
Li, Ping
Chappell, Mark C.
Venue: Hypertension
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1999-01
Volume: 33
Issue: 1
Pages: 323-328
ISSN: 0194-911X (ISSN-L)
1524-4563
DOI: 10.1161/01.hyp.33.1.323
OpenAlex: W2167128829
Cited by: 290
References: 54
Citations by year: 2026: 3 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 8 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 11 · 2017: 9 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 7
FWCI: 8.73
Type: journal article
Language: en
Open access: closed
Locations: Hypertension (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association (HL-56973)
National Institutes of Health (HL‐56973)
National Heart, Lung, and Blood Institute (R29HL056973, HL56973)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords: estrogen, angiotensin-converting enzyme, estradiol, estrogen replacement therapy, angiotensin II, postmenopausal women, cardioprotection, renal cortex, renal medulla, lung, aorta, angiotensin-(1-7), bradykinin, ovariectomy
MeSH terms: Animals, Aorta, Estradiol, Female, Gene Expression Regulation, Humans, Kidney Cortex, Kidney Medulla, Peptidyl-Dipeptidase A, Lung, Muscle, Smooth, Vascular, Ovariectomy, RNA, Messenger, Transcription, Genetic, Estrogen Replacement Therapy, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Rats

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Estrogen Regulation of Angiotensin-Converting Enzyme mRNA

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