Imidapril treatment improves the attenuated inotropic and intracellular calcium responses to ATP in heart failure due to myocardial infarction
Article first published online: 29 JAN 2009
2005 British Pharmacological Society
British Journal of Pharmacology
Volume 144, Issue 2, pages 202–211, January 2005
How to Cite
Saini, H. K., Shao, Q., Musat, S., Takeda, N., Tappia, P. S. and Dhalla, N. S. (2005), Imidapril treatment improves the attenuated inotropic and intracellular calcium responses to ATP in heart failure due to myocardial infarction. British Journal of Pharmacology, 144: 202–211. doi: 10.1038/sj.bjp.0705867
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received February 3, 2004, Revised April 28, 2004, Accepted May 7, 2004)
- ATP-mediated responses;
- congestive heart failure;
- isolated cardiomyocytes;
- intracellular calcium;
- angiotensin blockade
- 1M Adenosine 5′-triphosphate (ATP) is known to augment cardiac contractile activity and cause an increase in intracellular Ca2+ concentration ([Ca2+]i) in isolated cardiomyocytes. However, no information regarding the ATP-mediated signal transduction in the myocardium in congestive heart failure (CHF) is available.
- 2CHF due to myocardial infarction (MI) in rats was induced by the occlusion of the left coronary artery for 8 weeks. The positive inotropy due to ATP was depressed in failing hearts. Treatment of 3 weeks infarcted animals with imidapril (1 mg kg−1 day−1) for a period of 5 weeks improved the left ventricle function and decreased the attenuation of inotropic response to ATP.
- 3ATP-induced increase in [Ca2+]i was significantly depressed in cardiomyocytes isolated from the failing heart and this change was partially attenuated by imidapril treatment. However, the binding characteristics of 35S-labeled adenosine 5′-(γ-thio) triphosphate in sarcolemma isolated from the failing heart remained unaltered.
- 4ATP-induced increase in [Ca2+]i was depressed by verapamil and cibacron blue in both control and failing heart cardiomyocytes; however, the ATP response in the failing hearts, unlike the control preparations, was not decreased by ryanodine. This insensitivity to ryanodine was attenuated by imidapril treatment.
- 5Treatment of infarcted rats with enalapril and losartan produced effects similar to imidapril.
- 6These findings indicate that the positive inotropic response to ATP and ATP-induced increase in [Ca2+]i in cardiomyocytes are impaired in heart failure. Furthermore, blockade of renin angiotensin system prevented the impairment of the ATP-mediated inotropic and [Ca2+]i responses in the failing heart.
British Journal of Pharmacology (2005) 144, 202–211. doi:10.1038/sj.bjp.0705867