| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print December 13, 2001
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00780.2001
Submitted on August 30, 2001
Accepted on December 7, 2001
1 Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, ND, USA
* To whom correspondence should be addressed. E-mail: jren{at}medicine.nodak.edu.
Chronic alcoholism contributes to the development of alcoholic cardiomyopathy, manifested as ventricular dilation and impaired ventricular contractility, however, its specific toxic mechanism is largely unknown. The present study examined the impact of cardiac-specific overexpression of alcohol dehydrogenase (ADH), which oxidizes ethanol into acetaldehyde (ACA), on the cardiac contractile response to externally administrated ethanol. Ventricular myocytes were isolated from adult ADH transgenic and age-matched wild-type (FVB) littermate. Mechanical and intracellular Ca2+ properties were measured with an IonOptix SoftEdge system. ACA production was assessed by gas chromatography. The ADH myocytes exhibited similar mechanical and intracellular Ca2+ properties but a far more efficient ability to convert ethanol into ACA compared to the FVB myocytes. Acute exposure to ethanol (80 - 640 mg/dl) elicited concentration-dependent decrease of cell shortening and intracellular Ca2+ transients in the FVB group with a maximal inhibition of 23.3% and 23.4%, respectively. Strikingly, the ethanol-induced depression on cell shortening and intracellular Ca2+ was significantly augmented in ADH group, with a maximal inhibition of 43.7% and 40.6%, respectively. Pretreatment with the ADH inhibitor 4-methylpyrazole (4-MP) or the aldehyde dehydrogenase inhibitor cyanamide prevented or augmented the ethanol-induced inhibition, respectively, in the ADH but not in the FVB group. The ADH transgene also substantiated the ethanol-induced inhibition on the maximal velocity of shortening/relengthening and unmasked an ethanol-induced prolongation of the duration of shortening and relengthening, which was abolished by 4-MP. These data suggest that elevated cardiac ACA exposure due to enhanced ADH expression may play an important role in the development of alcoholic cardiomyopathy.
This article has been cited by other articles:
|
|
 |
|
  D. N. Charo, M. Ho, G. Fajardo, M. Kawana, R. K. Kundu, A. Y. Sheikh, T. P. Finsterbach, N. J. Leeper, K. V. Ernst, M. M. Chen, et al. Endogenous regulation of cardiovascular function by apelin-APJ Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1904 - H1913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Laonigro, M. Correale, M. Di Biase, and E. Altomare Alcohol abuse and heart failure Eur J Heart Fail, May 1, 2009; 11(5): 453 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Doser, S. Turdi, D. P. Thomas, P. N. Epstein, S.-Y. Li, and J. Ren Transgenic Overexpression of Aldehyde Dehydrogenase-2 Rescues Chronic Alcohol Intake-Induced Myocardial Hypertrophy and Contractile Dysfunction Circulation, April 14, 2009; 119(14): 1941 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Oba, Y. Maeno, M. Nagao, N. Sakuma, and T. Murayama Cellular redox state protects acetaldehyde-induced alteration in cardiomyocyte function by modifying Ca2+ release from sarcoplasmic reticulum Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H121 - H133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, S. Wu, S.-Y. Li, F. L. Lopez, M. Du, J. Kajstura, P. Anversa, and J. Ren Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1398 - H1403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, F. Dong, Q. Li, A. J. Borgerding, A. L. Klein, and J. Ren Cardiac overexpression of catalase antagonizes ADH-associated contractile depression and stress signaling after acute ethanol exposure in murine myocytes J Appl Physiol, December 1, 2005; 99(6): 2246 - 2254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. MacGowan, J. Rager, S. G. Shroff, and M. A. Mathier In vivo {alpha}-adrenergic responses and troponin I phosphorylation: anesthesia interactions J Appl Physiol, April 1, 2005; 98(4): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Oba and Y. Maeno Acetaldehyde alters Ca2+-release channel gating and muscle contraction in a dose-dependent manner Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1188 - C1194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Duan, H.-Y. Zhang, S. D. Adkins, B. H. Ren, F. L. Norby, X. Zhang, J. N. Benoit, P. N. Epstein, and J. Ren Impaired cardiac function and IGF-I response in myocytes from calmodulin-diabetic mice: role of Akt and RhoA Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E366 - E376. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
