(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
This article has been cited by other articles:
 |
|
 |
|
  E. L. Schopick, N. D. Fisher, J. Lin, J. P. Forman, and G. C. Curhan Post-menopausal hormone use and albuminuria Nephrol. Dial. Transplant., December 1, 2009; 24(12): 3739 - 3744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Lindsey, J. A. Cohen, K. B. Brosnihan, P. E. Gallagher, and M. C. Chappell Chronic Treatment with the G Protein-Coupled Receptor 30 Agonist G-1 Decreases Blood Pressure in Ovariectomized mRen2.Lewis Rats Endocrinology, August 1, 2009; 150(8): 3753 - 3758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ricchiuti, C. G Lian, E. M Oestreicher, L. Tran, J. R Stone, T. Yao, E. W Seely, G. H Williams, and G. K Adler Estradiol increases angiotensin II type 1 receptor in hearts of ovariectomized rats J. Endocrinol., January 1, 2009; 200(1): 75 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Coimbra, L. S. Sanchez, J. M. Potenza, L. V. Rossoni, S. L. Amaral, and L. C. Michelini Is Gender Crucial for Cardiovascular Adjustments Induced by Exercise Training in Female Spontaneously Hypertensive Rats? Hypertension, September 1, 2008; 52(3): 514 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Ojeda, D. Grigore, and B. T. Alexander Developmental Programming of Hypertension: Insight From Animal Models of Nutritional Manipulation Hypertension, July 1, 2008; 52(1): 44 - 50. [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Miller and S. P. Duckles Vascular Actions of Estrogens: Functional Implications Pharmacol. Rev., June 1, 2008; 60(2): 210 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Brosnihan, J. B. Hodgin, O. Smithies, N. Maeda, and P. Gallagher Tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor-{alpha} knock-out mice Exp Physiol, May 1, 2008; 93(5): 658 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Brosnihan, P. Li, J. P. Figueroa, D. Ganten, and C. M. Ferrario Estrogen, nitric oxide, and hypertension differentially modulate agonist-induced contractile responses in female transgenic (mRen2)27 hypertensive rats Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H1995 - H2001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. A. Neves, K. Stovall, J. Joyner, G. Valdes, P. E. Gallagher, C. M. Ferrario, D. C. Merrill, and K. B. Brosnihan ACE2 and ANG-(1-7) in the rat uterus during early and late gestation Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R151 - R161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. de Souza Mecawi, A. Lepletier, I. Gomes de Araujo, E. Lopes Olivares, and L. C. Reis Assessment of brain AT1-receptor on the nocturnal basal and angiotensin-induced thirst and sodium appetite in ovariectomised rats Journal of Renin-Angiotensin-Aldosterone System, December 1, 2007; 8(4): 169 - 175. [Abstract] [PDF]
|
|
|
|
|
|
N. B. Ojeda, D. Grigore, E. B. Robertson, and B. T. Alexander Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring Hypertension, October 1, 2007; 50(4): 679 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Joyner, L. A. A. Neves, J. P. Granger, B. T. Alexander, D. C. Merrill, M. C. Chappell, C. M. Ferrario, W. P. Davis, and K. B. Brosnihan Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R169 - R177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Watkins, D. Platt, T. Papenbrock, A. Wilkins, J. J. Eckert, W. Y. Kwong, C. Osmond, M. Hanson, and T. P. Fleming From the Cover: Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure PNAS, March 27, 2007; 104(13): 5449 - 5454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sakima, D. B. Averill, S. O. Kasper, L. Jackson, D. Ganten, C. M. Ferrario, P. E. Gallagher, and D. I. Diz Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1412 - H1419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Deschepper and B. Llamas Hypertensive Cardiac Remodeling in Males and Females: From the Bench to the Bedside Hypertension, March 1, 2007; 49(3): 401 - 407. [Full Text] [PDF]
|
|
|
|
|
|
M. C. Chappell, L. M. Yamaleyeva, and B. M. Westwood Estrogen and salt sensitivity in the female mRen(2).Lewis rat Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1557 - R1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ito, Y. Hirooka, Y. Kimura, Y. Sagara, and K. Sunagawa Ovariectomy Augments Hypertension Through Rho-Kinase Activation in the Brain Stem in Female Spontaneously Hypertensive Rats Hypertension, October 1, 2006; 48(4): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Yanes, D. G. Romero, J. W. Iles, R. Iliescu, C. Gomez-Sanchez, and J. F. Reckelhoff Sexual dimorphism in the renin-angiotensin system in aging spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R383 - R390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Valencia, G. Pacheco-Rodriguez, A. K. Carmona, J. Xavier, P. Bruneval, W. K. Riemenschneider, Y. Ikeda, Z.-X. Yu, V. J. Ferrans, and J. Moss Tissue-Specific Renin-Angiotensin System in Pulmonary Lymphangioleiomyomatosis Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 40 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Dean, J. Tan, R. White, E. R. O'Brien, and F. H. H. Leenen Regulation of components of the brain and cardiac renin-angiotensin systems by 17beta-estradiol after myocardial infarction in female rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R155 - R162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni, D. Hunt, K. Chen, T. Emmett, and G. Kargacin Differential autocrine modulation of atrial and ventricular potassium currents and of oxidative stress in diabetic rats Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1879 - H1888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y Shimoni, D Hunt, M Chuang, K. Y Chen, G Kargacin, and D. L Severson Modulation of potassium currents by angiotensin and oxidative stress in cardiac cells from the diabetic rat J. Physiol., August 15, 2005; 567(1): 177 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sakima, D. B. Averill, P. E. Gallagher, S. O. Kasper, E. N. Tommasi, C. M. Ferrario, and D. I. Diz Impaired Heart Rate Baroreflex in Older Rats: Role of Endogenous Angiotensin-(1-7) at the Nucleus Tractus Solitarii Hypertension, August 1, 2005; 46(2): 333 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tsuda, M. Iwai, J.-M. Li, H.-S. Li, L.-J. Min, A. Ide, M. Okumura, J. Suzuki, M. Mogi, H. Suzuki, et al. Inhibitory Effects of AT1 Receptor Blocker, Olmesartan, and Estrogen on Atherosclerosis Via Anti-Oxidative Stress Hypertension, April 1, 2005; 45(4): 545 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Dean, J. Tan, E. R. O'Brien, and F. H. H. Leenen 17{beta}-Estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R759 - R766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Reckelhoff Sex Steroids, Cardiovascular Disease, and Hypertension: Unanswered Questions and Some Speculations Hypertension, February 1, 2005; 45(2): 170 - 174. [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Gallagher and E.A. Tallant Inhibition of human lung cancer cell growth by angiotensin-(1-7) Carcinogenesis, November 1, 2004; 25(11): 2045 - 2052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni and X.-F. Liu Gender differences in ANG II levels and action on multiple K+ current modulation pathways in diabetic rats Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H311 - H319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Chaves, D. Corella, J. V. Sorli, P. Marin-Garcia, M. Guillen, and J. Redon Polymorphisms of the Renin-Angiotensin System Influence Height in Normotensive Women in a Spanish Population J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2301 - 2305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishiyama, P. E. Gallagher, D. B. Averill, E. A. Tallant, K. B. Brosnihan, and C. M. Ferrario Upregulation of Angiotensin-Converting Enzyme 2 After Myocardial Infarction by Blockade of Angiotensin II Receptors Hypertension, May 1, 2004; 43(5): 970 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Modrall, J. Sadjadi, K. B. Brosnihan, P. E. Gallagher, C.-h. Yu, G. L. Kramer, K. E. Bernstein, and M. C. Chappell Depletion of Tissue Angiotensin-Converting Enzyme Differentially Influences the Intrarenal and Urinary Expression of Angiotensin Peptides Hypertension, April 1, 2004; 43(4): 849 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Ahmed, A. K. Kang, K. D. Burns, C. R. J. Kennedy, V. Lai, D. C. Cattran, J. W. Scholey, and J. A. Miller Effects of Oral Contraceptive Use on the Renal and Systemic Vascular Response to Angiotensin II Infusion J. Am. Soc. Nephrol., March 1, 2004; 15(3): 780 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni, M. Chuang, E. D. Abel, and David. L. Severson Gender-dependent attenuation of cardiac potassium currents in type 2 diabetic db/db mice J. Physiol., March 1, 2004; 555(2): 345 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Owonikoko, M. E. Fabucci, P. R. Brown, N. Nisar, J. Hilton, W. B. Mathews, H. T. Ravert, P. Rauseo, K. Sandberg, R. F. Dannals, et al. In Vivo Investigation of Estrogen Regulation of Adrenal and Renal Angiotensin (AT1) Receptor Expression by PET J. Nucl. Med., January 1, 2004; 45(1): 94 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Brosnihan, L. A.A. Neves, J. Joyner, D. B. Averill, M. C. Chappell, R. Sarao, J. Penninger, and C. M. Ferrario Enhanced Renal Immunocytochemical Expression of ANG-(1-7) and ACE2 During Pregnancy Hypertension, October 1, 2003; 42(4): 749 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Chappell, P. E. Gallagher, D. B. Averill, C. M. Ferrario, and K. B. Brosnihan Estrogen or the AT1 Antagonist Olmesartan Reverses the Development of Profound Hypertension in the Congenic mRen2.Lewis Rat Hypertension, October 1, 2003; 42(4): 781 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. A. Neves, A. F. Williams, D. B. Averill, C. M. Ferrario, M. P. Walkup, and K. B. Brosnihan Pregnancy Enhances the Angiotensin (Ang)-(1-7) Vasodilator Response in Mesenteric Arteries and Increases the Renal Concentration and Urinary Excretion of Ang-(1-7) Endocrinology, August 1, 2003; 144(8): 3338 - 3343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni and X.-F. Liu Sex differences in the modulation of K+ currents in diabetic rat cardiac myocytes J. Physiol., July 15, 2003; 550(2): 401 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wu, C. Maric, D. M. Roesch, W. Zheng, J. G. Verbalis, and K. Sandberg Estrogen Regulates Adrenal Angiotensin AT1 Receptors by Modulating AT1 Receptor Translation Endocrinology, July 1, 2003; 144(7): 3251 - 3261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xu, I. A Arenas, S. J Armstrong, and S. T Davidge Estrogen modulation of left ventricular remodeling in the aged heart Cardiovasc Res, February 1, 2003; 57(2): 388 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Tofovic, R. Dubey, E. M. Salah, and E. K. Jackson 2-Hydroxyestradiol Attenuates Renal Disease in Chronic Puromycin Aminonucleoside Nephropathy J. Am. Soc. Nephrol., November 1, 2002; 13(11): 2737 - 2747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Freshour, S. E. Chase, and K. L. Vikstrom Gender differences in cardiac ACE expression are normalized in androgen-deprived male mice Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1997 - H2003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Moreau, A. J. Donato, D. R. Seals, F. A. Dinenno, S. D. Blackett, G. L. Hoetzer, C. A. Desouza, and H. Tanaka Arterial intima-media thickness: site-specific associations with HRT and habitual exercise Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1409 - H1417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Redfield, R. J. Rodeheffer, S. J. Jacobsen, D. W. Mahoney, K. R. Bailey, and J. C. Burnett Jr Plasma brain natriuretic peptide concentration: impact of age and gender J. Am. Coll. Cardiol., September 4, 2002; 40(5): 976 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fischer, A. Baessler, and H. Schunkert Renin angiotensin system and gender differences in the cardiovascular system Cardiovasc Res, February 15, 2002; 53(3): 672 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Dubey, S. Oparil, B. Imthurn, and E. K. Jackson Sex hormones and hypertension Cardiovasc Res, February 15, 2002; 53(3): 688 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Mercier, F. Colombo, S. Mader, and A. Calderone Ovarian hormones induce TGF-{beta}3 and fibronectin mRNAs but exhibit a disparate action on cardiac fibroblast proliferation Cardiovasc Res, February 15, 2002; 53(3): 728 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takeda-Matsubara, H. Nakagami, M. Iwai, T.-X. Cui, T. Shiuchi, M. Akishita, C. Nahmias, M. Ito, and M. Horiuchi Estrogen Activates Phosphatases and Antagonizes Growth-Promoting Effect of Angiotensin II Hypertension, January 1, 2002; 39(1): 41 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Lewis, M. P. Bracamonte, K. S. Rud, and V. M. Miller Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Effects of sex and ovariectomy on responses to platelets in porcine femoral veins J Appl Physiol, December 1, 2001; 91(6): 2823 - 2830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Day, Y. Yang, Y. J. Suzuki, J. Stevens, R. Pathi, A. Perlmutter, B. L. Fanburg, and J. J. Lanzillo Bleomycin Upregulates Gene Expression of Angiotensin-Converting Enzyme via Mitogen-Activated Protein Kinase and Early Growth Response 1 Transcription Factor Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 613 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cyr, Y. Lepage, C. Blais Jr., N. Gervais, M. Cugno, J.-L. Rouleau, and A. Adam Bradykinin and des-Arg9-bradykinin metabolic pathways and kinetics of activation of human plasma Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H275 - H283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Woods, G. Onambele, R. Woledge, D. Skelton, S. Bruce, S. E. Humphries, and H. Montgomery Angiotensin-I Converting Enzyme Genotype-Dependent Benefit from Hormone Replacement Therapy in Isometric Muscle Strength and Bone Mineral Density J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2200 - 2204. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Roesch, Y. Tian, W. Zheng, M. Shi, J. G. Verbalis, and K. Sandberg Estradiol Attenuates Angiotensin-Induced Aldosterone Secretion in Ovariectomized Rats Endocrinology, December 1, 2000; 141(12): 4629 - 4636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Reckelhoff, H. Zhang, and K. Srivastava Gender Differences in Development of Hypertension in Spontaneously Hypertensive Rats : Role of the Renin-Angiotensin System Hypertension, January 1, 2000; 35(1): 480 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V M Miller Gender and vascular reactivity Lupus, June 1, 1999; 8(5): 409 - 415. [Abstract] [PDF]
|
|