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Imidapril treatment improves the attenuated inotropic and intracellular calcium responses to ATP in heart failure due to myocardial infarction
Author(s) -
Saini Harjot K,
Shao Qiming,
Musat Sorin,
Takeda Nobuakira,
Tappia Paramjit S,
Dhalla Naranjan S
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705867
Subject(s) - medicine , heart failure , enalapril , inotrope , endocrinology , cardiology , sarcolemma , ryanodine receptor , ventricle , angiotensin converting enzyme , chemistry , myocyte , calcium , blood pressure
1 M Adenosine 5′‐triphosphate (ATP) is known to augment cardiac contractile activity and cause an increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) in isolated cardiomyocytes. However, no information regarding the ATP‐mediated signal transduction in the myocardium in congestive heart failure (CHF) is available. 2 CHF 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. 3 ATP‐induced increase in [Ca 2+ ] 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 35 S‐labeled adenosine 5′‐( γ ‐thio) triphosphate in sarcolemma isolated from the failing heart remained unaltered. 4 ATP‐induced increase in [Ca 2+ ] 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. 5 Treatment of infarcted rats with enalapril and losartan produced effects similar to imidapril. 6 These findings indicate that the positive inotropic response to ATP and ATP‐induced increase in [Ca 2+ ] i in cardiomyocytes are impaired in heart failure. Furthermore, blockade of renin angiotensin system prevented the impairment of the ATP‐mediated inotropic and [Ca 2+ ] i responses in the failing heart.British Journal of Pharmacology (2005) 144 , 202–211. doi: 10.1038/sj.bjp.0705867