© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy
aCardiology Section, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1045, USA
bMerck and Co., Inc., Merck Research Laboratories, West Point, PA 19486, USA
* Corresponding author. Tel.: +33-6-716-2887; Fax: +33-6-716-9188.
Objective: The positive inotropic effect of endothelin-1 (ET-1) on normal myocardial contraction may be altered in pathological states. The purpose of this study was to assess the direct effect of ET-1 on cardiomyocyte performance and its cellular mechanism in congestive heart failure (CHF). Methods: We measured the plasma levels of ET-1 and compared the effects of ET-1 (10–10–10–8 M) on contractile performance and the [Ca2+]i transient in the myocytes of left ventricles (LV) from 15 age-matched normal adult rats and 15 rats with isoproterenol (ISO)-induced CHF. Results: With CHF, the plasma levels of ET-1 (19.7±6.3 vs. 4.1±0.5 fmol/ml, p<0.05) were markedly elevated. In normal myocytes, superfusion of ET-1 caused significant increases in the systolic amplitude (SA, 8–16%) and the peak velocity of shortening (dL/dtmax, 20–35%; p<0.01) without causing a change in the peak [Ca2+]i transient. In contrast, in myocytes from CHF rats, ET-1 produced significant reductions in SA (9–13%) and in the velocity of relengthening, dR/dtmax (10–14%; p<0.05). The myocytes' dR/dtmax also decreased by 8–10% (p<0.05). These changes were associated with a significant decrease in the peak [Ca2+]i transient (20–23%, p<0.0 1). These responses to ET-1 were abolished by the incubation of myocytes with an ETA receptor antagonist (BQ123) or a protein kinase C (PKC) inhibitor (H-7 or staurosporine). Conclusion: ISO-induced CHF is associated with elevated plasma ET-1 and an altered cardiomyocyte response to ET-1. After CHF, ET-1 produces a direct depression of cardiomyocyte contractile performance that is associated with a significant decrease in the peak [Ca2+]i transient. These effects are likely to be mediated through ETA receptors and involve the PKC pathway.
KEYWORDS Rat; Isoproterenol; Congestive heart failure; Endothelin-1; Contraction; Relaxation; Cardiomyocyte; [Ca2+]i transient, Na+–H+ exchange; Protein kinase C
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Y. Chung, M. Kang, and J. W. Walker Contractile regulation by overexpressed ETA requires intact T tubules in adult rat ventricular myocytes Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2391 - H2399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kang, K. Y. Chung, and J. W. Walker G-Protein Coupled Receptor Signaling in Myocardium: Not for the Faint of Heart Physiology, June 1, 2007; 22(3): 174 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. E. Osadchii, G. R. Norton, R. McKechnie, D. Deftereos, and A. J. Woodiwiss Cardiac dilatation and pump dysfunction without intrinsic myocardial systolic failure following chronic beta-adrenoreceptor activation Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1898 - H1905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-S. Zhang, H.-J. Cheng, K. Onishi, N. Ohte, T. Wannenburg, and C.-P. Cheng Enhanced Inhibition of L-type Ca2+ Current by {beta}3-Adrenergic Stimulation in Failing Rat Heart J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1203 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Morimoto, H. Hasegawa, H.-J. Cheng, W. C. Little, and C.-P. Cheng Endogenous {beta}3-adrenoreceptor activation contributes to left ventricular and cardiomyocyte dysfunction in heart failure Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2425 - H2433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Azeka, J. A. Franchini Ramires, C. Valler, and E. Alcides Bocchi Delisting of infants and children from the heart transplantation waiting list after carvedilol treatment J. Am. Coll. Cardiol., December 4, 2002; 40(11): 2034 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Spinale The bioactive peptide endothelin causes multiple biologic responses relevant to myocardial and vascular performance after cardiac surgery J. Thorac. Cardiovasc. Surg., June 1, 2002; 123(6): 1031 - 1034. [Full Text] [PDF]
|
|
|
|
|
|
Z.-S. Zhang, H.-J. Cheng, T. Ukai, H. Tachibana, and C.-P. Cheng Enhanced Cardiac L-Type Calcium Current Response to beta 2-Adrenergic Stimulation in Heart Failure J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 188 - 196. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Packer, A. J.S. Coats, M. B. Fowler, H. A. Katus, H. Krum, P. Mohacsi, J. L. Rouleau, M. Tendera, A. Castaigne, E. B. Roecker, et al. Effect of Carvedilol on Survival in Severe Chronic Heart Failure N. Engl. J. Med., May 31, 2001; 344(22): 1651 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-P. Cheng, T. Ukai, K. Onishi, N. Ohte, M. Suzuki, Z.-S. Zhang, H.-J. Cheng, H. Tachibana, A. Igawa, and W. C. Little The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1853 - H1860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Walker, S. C. Baicu, A. T. Goldberg, C. E. Widener, D. J. Fary, D. K. Almany, A. Ergul, F. A. Crawford Jr, and F. G. Spinale Temporal endothelin dynamics of the myocardial interstitium and systemic circulation in cardiopulmonary bypass J. Thorac. Cardiovasc. Surg., November 1, 2000; 120(5): 864 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-T. Shen, P. S Buie, J. J Lynch, S. M Krause, and X.-L. Ma Chronic therapy with an ETA/B receptor antagonist in conscious dogs during progression of congestive heart failure: Intracellular Ca2+ regulation and nitric oxide mediated coronary relaxation Cardiovasc Res, November 1, 2000; 48(2): 332 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ergul, C. A. Walker, A. Goldberg, S. C. Baicu, J. W. Hendrick, M. K. King, and F. G. Spinale ET-1 in the myocardial interstitium: relation to myocyte ECE activity and expression Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2050 - H2056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Onishi, M. Ohno, W. C. Little, and C.-P. Cheng Endogenous Endothelin-1 Depresses Left Ventricular Systolic and Diastolic Performance in Congestive Heart Failure J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1214 - 1222. [Abstract] [Full Text]
|
|
|
|
 |
|
 H.-J. Cheng, Z.-S. Zhang, K. Onishi, T. Ukai, D. C. Sane, and C.-P. Cheng Upregulation of Functional {beta}3-Adrenergic Receptor in the Failing Canine Myocardium Circ. Res., September 28, 2001; 89(7): 599 - 606. [Abstract] [Full Text] [PDF]
|
|