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(Circulation. 1999;99:2694-2701.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Activation of Cardiac Aldosterone Production in Rat Myocardial Infarction
Effect of Angiotensin II Receptor Blockade and Role in Cardiac Fibrosis
From INSERM U127, IFR Circulation, Université D. Diderot, and Service de Biochimie, CHU Pitié-Salpétrière (B.A.-F., A.C.), Paris, France.
Correspondence to Claude Delcayre, U127-INSERM, Hôpital Lariboisière, 41 Boulevard de la Chapelle, 75475 Paris Cedex 10, France. E-mail delcayre{at}infobiogen.fr
Background—This study analyzed the regulation and the role of the cardiac steroidogenic system in myocardial infarction (MI).
Methods and Results—Seven days after MI, rats were randomized to untreated infarcted group or spironolactone- (20 and 80 mg · kg-1 · d-1), losartan- (8 mg · kg-1 · d-1), spironolactone plus losartan–, and L-NAME– (5 mg · kg-1 · d-1) treated infarcted groups for 25 days. Sham-operated rats served as controls. In the noninfarcted myocardium of the left ventricle (LV), MI raised aldosterone synthase mRNA (the terminal enzyme of aldosterone synthesis) by 2.0-fold and the aldosterone level by 3.7-fold. Conversely, MI decreased 11ß-hydroxylase mRNA (the terminal enzyme of corticosterone synthesis) by 2.4-fold and the corticosterone level by 1.9-fold. MI also induced a 1.9-fold increase in cardiac angiotensin II level. Such cardiac regulations were completely prevented by treatment of the infarcted heart with losartan. The MI-induced collagen deposition in noninfarcted LV myocardium was prevented by 1.6-fold by both low and high doses of spironolactone and by 2.5-fold by losartan. In addition, norepinephrine level was unchanged in infarcted heart but was attenuated by both losartan and spironolactone treatments.
Conclusions—MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This increase is mediated primarily by cardiac angiotensin II via AT1-subtype receptor and may be involved in post-MI ventricular fibrosis and in control of tissue norepinephrine concentration.
Key Words: myocardial infarction • aldosterone • angiotensin • collagen
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A. Fiebeler, F. Schmidt, D. N. Muller, J.-K. Park, R. Dechend, M. Bieringer, E. Shagdarsuren, V. Breu, H. Haller, and F. C. Luft Mineralocorticoid Receptor Affects AP-1 and Nuclear Factor-{{kappa}}B Activation in Angiotensin II-Induced Cardiac Injury Hypertension, February 1, 2001; 37(2): 787 - 793. [Abstract] [Full Text] [PDF]
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Y. Mizuno, M. Yoshimura, H. Yasue, T. Sakamoto, H. Ogawa, K. Kugiyama, E. Harada, M. Nakayama, S. Nakamura, T. Ito, et al. Aldosterone Production Is Activated in Failing Ventricle in Humans Circulation, January 2, 2001; 103(1): 72 - 77. [Abstract] [Full Text] [PDF]
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J. Bauersachs, D. Fraccarollo, G. Ertl, N. Gretz, M. Wehling, and M. Christ Striking Increase of Natriuresis by Low-Dose Spironolactone in Congestive Heart Failure Only in Combination With ACE Inhibition : Mechanistic Evidence to Support RALES Circulation, November 7, 2000; 102(19): 2325 - 2328. [Abstract] [Full Text] [PDF]
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Y. Takeda, T. Yoneda, M. Demura, I. Miyamori, and H. Mabuchi Cardiac Aldosterone Production in Genetically Hypertensive Rats Hypertension, October 1, 2000; 36(4): 495 - 500. [Abstract] [Full Text] [PDF]
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M. V. Cohen, X.-M. Yang, T. Neumann, G. Heusch, and J. M. Downey Favorable Remodeling Enhances Recovery of Regional Myocardial Function in the Weeks After Infarction in Ischemically Preconditioned Hearts Circulation, August 1, 2000; 102(5): 579 - 583. [Abstract] [Full Text] [PDF]
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K. M. Kayes-Wandover and P. C. White Steroidogenic Enzyme Gene Expression in the Human Heart J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2519 - 2525. [Abstract] [Full Text]
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M. G. St. J. Sutton and N. Sharpe Left Ventricular Remodeling After Myocardial Infarction : Pathophysiology and Therapy Circulation, June 27, 2000; 101(25): 2981 - 2988. [Full Text] [PDF]
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L. Mandinov, F. R. Eberli, C. Seiler, and O. M. Hess Diastolic heart failure Cardiovasc Res, March 1, 2000; 45(4): 813 - 825. [Abstract] [Full Text] [PDF]
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H. Yoshida and M. Karmazyn Na+/H+ exchange inhibition attenuates hypertrophy and heart failure in 1-wk postinfarction rat myocardium Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H300 - H304. [Abstract] [Full Text] [PDF]
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J.-P. Benitah and G. Vassort Aldosterone Upregulates Ca2+ Current in Adult Rat Cardiomyocytes Circ. Res., December 3, 1999; 85(12): 1139 - 1145. [Abstract] [Full Text] [PDF]
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