The DOI matches its Crossref record; 52 of the 54 references it cites were found in a registry or an index.
Estrogen Regulation of Angiotensin-Converting Enzyme mRNA
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).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Researchers have reported that both ACE expression and activity are inhibited by estrogen in rodent models [26-29].”
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Plasma APP activity has been shown to form a continuous distribution in the general population (Cyr et al. 2001), suggesting that plasma APP activity is a complex quantitative trait likely influenced by multiple genetic loci and nongenetic factors (e.g., smoking and hormone replacement therapy [Gallagher et al. 1999]).”
From A variant in XPNPEP2 is associated with angioedema induced by angiotensin I-converting enzyme inhibitors. (2005) · cites this paper as Gallagher et al. 1999
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
Valery (1995) · doi:10.1001/jama.1995.03520270033028 · Cited by 2,320
Hypertension : pathophysiology, diagnosis, and management
Laragh, J. H., & Brenner, B. M. (1995) · Raven Press eBooks · Cited by 1,932
Differential Ligand Activation of Estrogen Receptors ERα and ERβ at AP1 Sites
Paech, K., Webb, P., Kuiper, G. G. J. M., Nilsson, S., Gustafsson, J.-Å., Kushner, P. J., & Scanlan, T. S. (1997) · Science · doi:10.1126/science.277.5331.1508 · Cited by 1,861
Stampfer, M. J., & Colditz, G. A. (1991) · Preventive Medicine · doi:10.1016/0091-7435(91)90006-p · Cited by 1,611
Butcher, R. L., COLLINS, W. E., & FUGO, N. W. (1974) · Endocrinology · doi:10.1210/endo-94-6-1704 · Cited by 1,313
Estrogen and coronary heart disease in women
Barrett-Connor, E. (1991) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1991.03460140089033 · Cited by 1,241
Activation of the ovalbumin gene by the estrogen receptor involves the Fos-Jun complex
Gaub, M., Gross-Bellard, M., Scheuer, I., Chambon, P., & Sassone‐Corsi, P. (1990) · Cell · doi:10.1016/0092-8674(90)90422-b · Cited by 467
Esther, C. R., Howard, T. E., Marino, E. M., Goddard, J. M., Capecchi, M. R., & Bernstein, K. E. (1996) · PubMed · Cited by 440
Effects of Estrogen Replacement Therapy on the Renin-Angiotensin System in Postmenopausal Women
Schunkert, H., Danser, A. H. J., Hense, H.-W., Derkx, F. H. M., Ku¨rzinger, S., & Riegger, G. A. J. (1997) · Circulation · doi:10.1161/01.cir.95.1.39 · Cited by 438
Hecker, M., Bara, A. T., Bauersachs, J. K., & Busse, R. (1994) · The Journal of Physiology · doi:10.1113/jphysiol.1994.sp020449 · Cited by 418
Angiotensin-(1-7) Dilates Canine Coronary Arteries Through Kinins and Nitric Oxide
Brosnihan, K. B., Li, P., & Ferrario, C. M. (1996) · Hypertension · doi:10.1161/01.hyp.27.3.523 · Cited by 405
Self-citationEstrogen and the blood vessel wall
Mendelsohn, M. E., & Karas, R. H. (1994) · Current Opinion in Cardiology · doi:10.1097/00001573-199409000-00018 · Cited by 310
Metabolism of Angiotensin-(1–7) by Angiotensin-Converting Enzyme
Chappell, M. C., Pirro, N. T., Sykes, A., & Ferrario, C. M. (1998) · Hypertension · doi:10.1161/01.hyp.31.1.362 · Cited by 288
Self-citationWelches, W. R., Brosnihan, K. B., & Ferrario, C. M. (1993) · Life Sciences · doi:10.1016/0024-3205(93)90108-f · Cited by 254
Self-citationWagner, J. D., Clarkson, T. B., Clair, R. W. S., Schwenke, D. C., Shively, C. A., & Adams, M. R. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115526 · Cited by 251
Li, P., Chappell, M. C., Ferrario, C. M., & Brosnihan, K. B. (1997) · Hypertension · doi:10.1161/01.hyp.29.1.394 · Cited by 245
Self-citationAndrogen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats.
Chen, Y., Naftilan, A. J., & Oparil, S. (1992) · Hypertension · doi:10.1161/01.hyp.19.5.456 · Cited by 245
Keaney, J. F., Shwaery, G. T., Xu, A., Nicolosi, R. J., Loscalzo, J., Foxall, T. L., & Vita, J. A. (1994) · Circulation · doi:10.1161/01.cir.89.5.2251 · Cited by 238
Cardiovascular disease in women
Castelli, W. P. (1988) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(88)90189-5 · Cited by 223
Prorenin in High Concentrations in Human Ovarian Follicular Fluid
Glorioso, N., Atlas, S. A., Laragh, J. H., Jewelewicz, R., & Sealey, J. E. (1986) · Science · doi:10.1126/science.3529392 · Cited by 213
Advances in Internal Medicine.
STURGIS, C. C., Davenport, F. M., Davey, W. N., Hoobler, S. W., Fd, J., POLLARD, H. M., & Jm, S. (1962) · Annals of Internal Medicine · doi:10.7326/0003-4819-57-5-864_3 · Cited by 189
Regression of Atherosclerosis in Female Monkeys
Williams, J. K., Anthony, M. S., Honoré, E. K., Herrington, D. M., Morgan, T. M., Register, T. C., & Clarkson, T. B. (1995) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.15.7.827 · Cited by 188
Pharmacokinetic and Pharmacologic Variation Between Different Estrogen Products
O’Connell, M. B. (1995) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1995.tb04143.x · Cited by 186
Lassegue, B. P., Alexander, R. W., Nickenig, G., Clark, M. A., Murphy, T. J., & Griendling, K. K. (1995) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10511-7 · Cited by 180
Uht, R. M., Anderson, C. M., Webb, P., & Kushner, P. J. (1997) · Endocrinology · doi:10.1210/endo.138.7.5244 · Cited by 162
Brosnihan, K. B., Li, P., Ganten, D., & Ferrario, C. M. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.273.6.r1908 · Cited by 156
Self-citationIncreased Expression of Endothelial Constitutive Nitric Oxide Synthase in Rat Aorta during Pregnancy
Goetz, R. M., Morano, I. L., Calovini, T., Studer, R., & Holtz, J. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2750 · Cited by 149
Howard, T. E., Balogh, R., Overbeek, P. A., & Bernstein, K. E. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.1.18 · Cited by 118
Recent advances in knowledge of the structure and function of the angiotensin I converting enzyme
Corvol, P. L., Michaud, A., Soubrier, F., & Williams, T. A. (1995) · Journal of Hypertension · doi:10.1097/00004872-199509003-00002 · Cited by 114
Zhou, Y., Sun, Z., Means, A. R., Sassone‐Corsi, P., & Bernstein, K. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12262 · Cited by 79
Seltzer, A. M., Pinto, J. E. B., Viglione, P. N., Corrêa, F. M. D. A., Libertun, C., Tsutsumi, K., Steele, M. K., & Saavedra, J. M. (2008) · Neuroendocrinology · doi:10.1159/000126157 · Cited by 79
Studies on angiotensinogen formation in a liver perfusion system.
Nasjletti, A., & Gm, M. (1972) · PubMed · Cited by 74
Effects of chronic hormone replacement on the renin–angiotensin system in cynomolgus monkeys
Brosnihan, K. B., Weddle, D., Anthony, M. S., Heise, C., Li, P., & Ferrario, C. M. (1997) · Journal of Hypertension · doi:10.1097/00004872-199715070-00003 · Cited by 70
Self-citationThe isolation of angiotensin-converting enzyme cDNA.
Bernstein, K. E., Martin, B. M., Bernstein, E. A., Linton, J. P., Striker, L. J., & Striker, G. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37909-2 · Cited by 69
Villard, E., & Soubrier, F. (1996) · Cardiovascular Research · doi:10.1016/s0008-6363(96)00170-8 · Cited by 59
Ovarian sex steroids and atherosclerosis
Riedel, M., Rafflenbeul, W., & Lichtlen, P. R. (1993) · Journal of Molecular Medicine · doi:10.1007/bf00186631 · Cited by 59
Intracranial Ependymomas of Childhood: Current Management Strategies
Smyth, M. D., Horn, B. N., Russo, C. L., & Berger, M. S. (2000) · Pediatric Neurosurgery · doi:10.1159/000028995 · Cited by 56
Dasarathy, Y., Lanzillo, J. J., & Fanburg, B. L. (1992) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1992.263.6.l645 · Cited by 47
Rat Ovarian Renin: Characterization and Changes during the Estrous Cycle*
Howard, R. B., Pucell, A. G., Bumpus, F. M., & Husain, A. (1988) · Endocrinology · doi:10.1210/endo-123-5-2331 · Cited by 46
Role of Endothelium-Derived Bradykinin in the Control of Vascular Tone
Hecker, M., Dambacher, T., & Busse, R. (1992) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199200209-00011 · Cited by 40
Shai, S., Langford, K. G., Martin, B. M., & Bernstein, K. E. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90640-9 · Cited by 35
Renin messenger RNA, detected by polymerase chain reaction, can be switched on in rat atrium
Lou, Y., Robinson, B. G., & MORRIS, B. J. (1993) · Journal of Hypertension · doi:10.1097/00004872-199303000-00003 · Cited by 35
Rubattu, S., Quimby, F. W., & Sealey, J. E. (1991) · Journal of Hypertension · doi:10.1097/00004872-199106000-00008 · Cited by 27
Roy, S., Kusari, J., Soffer, R. L., Lai, C. Y., & Sen, G. C. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80548-5 · Cited by 24
Goraya, T., Kessler, S. P., Kumar, R. S., Douglas, J. G., & Sen, G. C. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.7.1194 · Cited by 22
The Influence of Normotensive Pregnancy and Pre‐Eclampsia on Angiotensin‐Converting Enzyme
Rasmussen, A. B., Pedersen, E. B., Rømer, F. K., Johannesen, P. L., Kristensen, S., Lauritsen, J. G., & Wohlert, M. (1983) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.3109/00016348309156235 · Cited by 20
Nucleotide sequence of rat elongation factor-1α cDNA
Shirasawa, T., Sakamoto, K., Akashi, T., Takahashi, H., & Kawashima, A. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.4.909 · Cited by 18
Serum Angiotensin-Converting Enzyme Activity in Pregnancy-Induced Hypertension
Li, J., Hu, H.-Y., & Zhao, Y. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000294867 · Cited by 17
Tallant, E. A., & Ferrario, C. M. (1996) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.5.9.1201 · Cited by 14
Wagner, J. D., Schwenke, D. C., Zhang, L., Applebaum-Bowden, D. M., Bagdade, J. D., & Adams, M. R. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.6.1128 · Cited by 14
Current and Future Therapeutic Approaches to Hyperlipidemia
Farmer, J. A., & Gotto, A. M. (1996) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60275-6 · Cited by 13
Flagged first, then by citations
2 of the 54 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019)
Umemura, S., Arima, H., Arima, S., Asayama, K., Dohi, Y., Hirooka, Y., Horio, T., Hoshide, S., Ikeda, S., Ishimitsu, T., et al. (2019) · Hypertension Research · doi:10.1038/s41440-019-0284-9 · Cited by 1,880
Physiology of Local Renin-Angiotensin Systems
Paul, M., Poyan Mehr, A., & Kreutz, R. (2006) · Physiological Reviews · doi:10.1152/physrev.00036.2005 · Cited by 1,739
Plasma brain natriuretic peptide concentration: impact of age and gender
Redfield, M. M., Rodeheffer, R. J., Jacobsen, S. J., Mahoney, D. W., Bailey, K. R., & Burnett, J. C. J. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02059-4 · Cited by 1,140
Iorga, A., Cunningham, C. M., Moazeni, S., Ruffenach, G., Umar, S., & Eghbali, M. (2017) · Biology of Sex Differences · doi:10.1186/s13293-017-0152-8 · Cited by 914
Mechanistic Pathways of Sex Differences in Cardiovascular Disease
Regitz‐Zagrosek, V., & Kararigas, G. (2016) · Physiological Reviews · doi:10.1152/physrev.00021.2015 · Cited by 758
Metadata
- Authors
- Gallagher, P. E., Li, P., Lenhart, J. R., Chappell, M. C., & Brosnihan, K. B.
- Affiliations
- Wake Forest University Health Sciences (US)
- Venue
- Hypertension
- Published
- 1999-01
- Volume
- 33
- Issue
- 1
- Pages
- 323-328
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
