期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 144, 期 2, 页码 202-211出版社
WILEY-BLACKWELL
DOI: 10.1038/sj.bjp.0705867
关键词
ATP-mediated responses; congestive heart failure; isolated cardiomyocytes; intracellular calcium; angiotensin blockade
1 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. 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 [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 S-35-labeled adenosine 5'-(gamma-thio) triphosphate in sarcolemma isolated from the failing heart remained unaltered. 4 ATP-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. 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 [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.
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