| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLE |
Baker Medical Research Institute (M.J.Y., L.M., R.D., J.W.F.), Melbourne Prahran 3181, Australia; and Prince Henry’s Institute of Medical Research (M.J.Y., J.W.F.), Clayton, Victoria 3168, Australia
In epithelial tissues such as kidney, mineralocorticoid receptors (MR) are protected against glucocorticoid occupancy by the enzyme 11ß-hydroxysteroid dehydrogenase (11ßHSD) type 2. If the enzyme is congenitally inactive, or blocked by carbenoxolone, physiologic glucocorticoids act as MR agonists in such tissues. In most nonepithelial tissues, including cardiomyocytes, 11ßHSD2 is expressed at minimal levels; in these tissues physiologic glucocorticoids act as MR antagonists, with the basis for this tissue selectivity currently unknown. Vascular smooth muscle cells (VSMC) express MR and 11ßHSD1/2, with 11ßHSD1 reported to show uncharacteristic oxidase activity, so that VSMC thus constitute a potential physiologic aldosterone target tissue. Because mineralocorticoid/salt administration triggers marked inflammatory responses in coronary vasculature, we reasoned that VSMC (like epithelial) MR may be activated by glucocorticoids if the protective enzyme is blocked. We thus gave uninephrectomized rats 0.9% NaCl solution to drink, and deoxycorticosterone (DOC, as a single 20 mg sc dose) or carbenoxolone (CBX, 2.5 mg/d in the drinking solution). Both DOC and CBX increased systolic blood pressure, heart, and kidney weight, and expression of cyclooxygenase 2, ED-1-positive macrophages, and osteopontin, with effects of both DOC and CBX blocked by the selective MR antagonist eplerenone. These findings suggest that local glucocorticoid excess, reflecting lower VSMC 11ßHSD1/2 activity may mimic systemic mineralocorticoid excess, and play a direct etiologic role in coronary vascular inflammatory responses under circumstances of a high salt intake.
This article has been cited by other articles:
 |
|
 |
|
  P. Klusonova, L. Rehakova, G. Borchert, K. Vagnerova, J. Neckar, P. Ergang, I. Miksik, F. Kolar, and J. Pacha Chronic Intermittent Hypoxia Induces 11{beta}-Hydroxysteroid Dehydrogenase in Rat Heart Endocrinology, September 1, 2009; 150(9): 4270 - 4277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Rickard, J. Morgan, G. Tesch, J. W. Funder, P. J. Fuller, and M. J. Young Deletion of Mineralocorticoid Receptors From Macrophages Protects Against Deoxycorticosterone/Salt-Induced Cardiac Fibrosis and Increased Blood Pressure Hypertension, September 1, 2009; 54(3): 537 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J Rickard and M. J Young Corticosteroid receptors, macrophages and cardiovascular disease J. Mol. Endocrinol., June 1, 2009; 42(6): 449 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Osmond and A. M. Dorrance 11{beta}-Hydroxysteroid Dehydrogenase Type II Inhibition Causes Cerebrovascular Remodeling and Increases Infarct Size after Cerebral Ischemia Endocrinology, February 1, 2009; 150(2): 713 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Michea, A. Villagran, A. Urzua, S. Kuntsmann, P. Venegas, L. Carrasco, M. Gonzalez, and E. T. Marusic Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats Hypertension, August 1, 2008; 52(2): 295 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Funder Mineralocorticoid Receptor Activation and Oxidative Stress Hypertension, November 1, 2007; 50(5): 840 - 841. [Full Text] [PDF]
|
|
|
|
|
|
A. J. Rickard, J. W. Funder, J. Morgan, P. J. Fuller, and M. J. Young Does Glucocorticoid Receptor Blockade Exacerbate Tissue Damage after Mineralocorticoid/Salt Administration? Endocrinology, October 1, 2007; 148(10): 4829 - 4835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Guder, J. Bauersachs, S. Frantz, D. Weismann, B. Allolio, G. Ertl, C. E. Angermann, and S. Stork Complementary and Incremental Mortality Risk Prediction by Cortisol and Aldosterone in Chronic Heart Failure Circulation, April 3, 2007; 115(13): 1754 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Fejes-Toth and A. Naray-Fejes-Toth Early Aldosterone-Regulated Genes in Cardiomyocytes: Clues to Cardiac Remodeling? Endocrinology, April 1, 2007; 148(4): 1502 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Funder Aldosterone and the Cardiovascular System: Genomic and Nongenomic Effects Endocrinology, December 1, 2006; 147(12): 5564 - 5567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Rickard, J. W. Funder, P. J. Fuller, and M. J. Young The Role of the Glucocorticoid Receptor in Mineralocorticoid/Salt-Mediated Cardiac Fibrosis Endocrinology, December 1, 2006; 147(12): 5901 - 5906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Reini, C. E. Wood, E. Jensen, and M. Keller-Wood Increased maternal cortisol in late-gestation ewes decreases fetal cardiac expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1708 - R1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Turchin, C. Z. Guo, G. K. Adler, V. Ricchiuti, I. S. Kohane, and G. H. Williams Effect of Acute Aldosterone Administration on Gene Expression Profile in the Heart Endocrinology, July 1, 2006; 147(7): 3183 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. M. Lam, J. W. Funder, D. J. Nikolic-Paterson, P. J. Fuller, and M. J. Young Mineralocorticoid Receptor Blockade But Not Steroid Withdrawal Reverses Renal Fibrosis in Deoxycorticosterone/Salt Rats Endocrinology, July 1, 2006; 147(7): 3623 - 3629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lister, D. J. Autelitano, A. Jenkins, R. D. Hannan, and K. E. Sheppard Cross talk between corticosteroids and alpha-adrenergic signalling augments cardiomyocyte hypertrophy: A possible role for SGK1 Cardiovasc Res, June 1, 2006; 70(3): 555 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C Shah, S. Pringle, and A. Struthers Aldosterone Blockade Over and Above ACE-Inhibitors in Patients with Coronary Artery Disease but without Heart Failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2006; 7(1): 20 - 30. [Abstract] [PDF]
|
|
|
|
|
|
P. J. Fuller and M. J. Young Mechanisms of Mineralocorticoid Action Hypertension, December 1, 2005; 46(6): 1227 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takai, D. Jin, M. Muramatsu, K. Kirimura, H. Sakonjo, and M. Miyazaki Eplerenone Inhibits Atherosclerosis in Nonhuman Primates Hypertension, November 1, 2005; 46(5): 1135 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sugiyama, T. Yoshimoto, K. Tsuchiya, N. Gochou, Y. Hirono, T. Tateno, N. Fukai, M. Shichiri, and Y. Hirata Aldosterone Induces Angiotensin Converting Enzyme Gene Expression via a JAK2-Dependent Pathway in Rat Endothelial Cells Endocrinology, September 1, 2005; 146(9): 3900 - 3906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M C Connell and E. Davies The new biology of aldosterone J. Endocrinol., July 1, 2005; 186(1): 1 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Salvi, C. Fiore, V. Battaglia, M. Palermo, D. Armanini, and A. Toninello Carbenoxolone Induces Oxidative Stress in Liver Mitochondria, Which Is Responsible for Transition Pore Opening Endocrinology, May 1, 2005; 146(5): 2306 - 2312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Tomlinson, E. A. Walker, I. J. Bujalska, N. Draper, G. G. Lavery, M. S. Cooper, M. Hewison, and P. M. Stewart 11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response Endocr. Rev., October 1, 2004; 25(5): 831 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zohar, B. Zhu, P. Liu, J. Sodek, and C. A. McCulloch Increased cell death in osteopontin-deficient cardiac fibroblasts occurs by a caspase-3-independent pathway Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1730 - H1739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Garnier, J. K. Bendall, S. Fuchs, B. Escoubet, F. Rochais, J. Hoerter, J. Nehme, M.-L. Ambroisine, N. De Angelis, G. Morineau, et al. Cardiac Specific Increase in Aldosterone Production Induces Coronary Dysfunction in Aldosterone Synthase-Transgenic Mice Circulation, September 28, 2004; 110(13): 1819 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Young and J. W. Funder Eplerenone, But Not Steroid Withdrawal, Reverses Cardiac Fibrosis in Deoxycorticosterone/ Salt-Treated Rats Endocrinology, July 1, 2004; 145(7): 3153 - 3157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Levy, R. Rocha, and J. W. Funder Distinguishing the Antihypertensive and Electrolyte Effects of Eplerenone J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2736 - 2740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. K Shieh, E. Kotlyar, and F. Sam Aldosterone and cardiovascular remodelling: focus on myocardial failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 3 - 13. [Abstract] [PDF]
|
|
|
|
 |
|
 W. Qin, A. E. Rudolph, B. R. Bond, R. Rocha, E. A.G. Blomme, J. J. Goellner, J. W. Funder, and E. G. McMahon Transgenic Model of Aldosterone-Driven Cardiac Hypertrophy and Heart Failure Circ. Res., July 11, 2003; 93(1): 69 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Funder Aldosterone Resurgens--Letter from EPHESUS J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2373 - 2375. [Full Text] [PDF]
|
|
|
|
|
|
P. C. White Aldosterone: Direct Effects on and Production by the Heart J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2376 - 2383. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
