(Circulation. 2000;102:253.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Reverse Remodeling of Cardiac Myocyte Hypertrophy in Hypertension and Failure by Targeting of the Renin-Angiotensin System
From the South Dakota Health Research Foundation, Cardiovascular Research Institute, Sioux Falls, SD 57105.
Correspondence to A. Martin Gerdes, PhD, South Dakota Health Research Foundation, Cardiovascular Research Institute, 1400 W 22nd St, Sioux Falls, SD 57105-1570. E-mail mgerdes{at}usd.edu
Background—ACE inhibitors (ACEIs) and angiotensin II type 1 (AT1) receptor blockers are effective in reducing left ventricular mass in hypertension and heart failure. However, the ability of these drugs to reverse excessive myocyte lengthening and transverse growth in heart failure is unknown.
Methods and Results—L-158,809 (an AT1 blocker; AT1), enalapril (an ACEI), and hydralazine (a vasodilator) were administered to spontaneously hypertensive heart failure rats between 6 and 10 months of age (early treatment) and between 18 and 22 months of age (late treatment). After 4 months of treatment, hemodynamics and chamber dimensions were collected before left ventricular myocyte isolation and subsequent analysis of myocyte shape. Each drug reduced systolic blood pressures to normal values. In the early and late studies, the ACEI reduced myocyte volume. Myocyte length was also reduced in the late study. However, the AT1 was most effective in reversing myocyte dimensions to near-normal values in both studies. Hydralazine was ineffective in reducing cell size but arrested progression of myocyte lengthening in the late study. Changes in myocyte shape reflected alterations in chamber dimensions and wall thickness.
Conclusions—Reversal of myocyte hypertrophy was produced in hypertensive/heart failure rats with an AT1. The ACEI was effective but to a lesser extent. Results indicate that it is possible to significantly reverse myocyte remodeling pharmacologically even if therapy is initiated near the onset of failure. Further work is needed to determine whether similar results can be obtained in humans.
Key Words: hypertension • drugs • heart failure • remodeling • myocytes
This article has been cited by other articles:
 |
|
 |
|
  J. A. Sharron, R. M. Esterl, W. K. Washburn, and G. A. Abrahamian Surgical Treatment of an Extrarenal Pseudoaneurysm After Kidney Transplantation Vascular and Endovascular Surgery, June 1, 2009; 43(3): 317 - 321. [Abstract] [PDF]
|
|
|
|
 |
|
 E. R. Lumbers, M. y. Kim, J. H. Burrell, V. Kumarasamy, A. C. Boyce, K. J. Gibson, K. L. Gatford, and J. A. Owens Effects of intrafetal IGF-I on growth of cardiac myocytes in late-gestation fetal sheep Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E513 - E519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Shuros, R. W. Salo, V. G. Florea, J. Pastore, M. A. Kuskowski, Y. Chandrashekhar, and I. S. Anand Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction Circulation, September 4, 2007; 116(10): 1162 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sridhar, S. J. Dech, V. A. Lacombe, T. S. Elton, S. A. McCune, R. A. Altschuld, and C. A. Carnes Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2192 - H2198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Thomas, J. A. Kuzman, B. E. Anderson, S. M. K. Andersen, E. H. Schlenker, M. S. Holder, and A. M. Gerdes Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2118 - H2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Hazinski, D. Markenson, S. Neish, M. Gerardi, J. Hootman, G. Nichol, H. Taras, R. Hickey, R. O'Connor, J. Potts, et al. Response to Cardiac Arrest and Selected Life-Threatening Medical Emergencies: The Medical Emergency Response Plan for Schools. A Statement for Healthcare Providers, Policymakers, School Administrators, and Community Leaders Pediatrics, January 1, 2004; 113(1): 155 - 168. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kacimi and A. M. Gerdes Alterations in G Protein and MAP Kinase Signaling Pathways During Cardiac Remodeling in Hypertension and Heart Failure Hypertension, April 1, 2003; 41(4): 968 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K.G Koshy, H. K Reddy, and H. H Shukla Collagen cross-linking: new dimension to cardiac remodeling Cardiovasc Res, March 1, 2003; 57(3): 594 - 598. [Full Text] [PDF]
|
|
|
|
|
|
T. Walther, A. Schubert, V. Falk, C. Binner, C. Walther, N. Doll, A. Fabricius, S. Dhein, J. Gummert, and F. W. Mohr Left Ventricular Reverse Remodeling After Surgical Therapy for Aortic Stenosis: Correlation to Renin-Angiotensin System Gene Expression Circulation, September 24, 2002; 106(12_suppl_1): I-23 - I-26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Radin, B. J. Holycross, L. C. Sharkey, L. Shiry, and S. A. McCune Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure J Appl Physiol, March 1, 2002; 92(3): 935 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, H. Chen, and J. L. Mehta Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells Hypertension, November 1, 2001; 38(5): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. Barone, R. W. Coatney, S. Chandra, S. K. Sarkar, A. H. Nelson, L. C. Contino, D. P. Brooks, W. G. Campbell Jr., E. H. Ohlstein, and R. N. Willette Eprosartan reduces cardiac hypertrophy, protects heart and kidney, and prevents early mortality in severely hypertensive stroke-prone rats Cardiovasc Res, June 1, 2001; 50(3): 525 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.H. Yacoub A novel strategy to maximize the efficacy of left ventricular assist devices as a bridge to recovery Eur. Heart J., April 1, 2001; 22(7): 534 - 540. [PDF]
|
|