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Keywords:

  • ATP-mediated responses;
  • congestive heart failure;
  • isolated cardiomyocytes;
  • intracellular calcium;
  • angiotensin blockade
  • 1
    M 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 35S-labeled adenosine 5′-(γ-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.

British Journal of Pharmacology (2005) 144, 202–211. doi:10.1038/sj.bjp.0705867