Protective Effect of Quinaprilat, an Active Metabolite of Quinapril, on Ca^<2+>-Overload Induced by Lysophosphatidylcholine in Isolated Rat Cardiomyocytes

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Abstract

We examined the effects of quinaprilat, an active metabolite of quinapril (an angiotensin converting enzyme (ACE) inhibitor) on the increase in intracellular concentration of Ca<SUP>2+</SUP> ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) (Ca<SUP>2+</SUP>-overload) induced by lysophosphatidylcholine (LPC) in isolated rat cardiomyocytes. LPC (15 μM) produced Ca<SUP>2+</SUP>-overload with a change in cell-shape from rod to round. Quinaprilat but not quinapril at 20 or 50 μM attenuated the LPC-induced increase in [Ca<SUP>2+</SUP>]<SUB>i</SUB> and the change in cell-shape in a concentration-dependent manner. Since quinaprilat has an inhibitory action on ACE and quinapril has practically no inhibitory action on ACE, it is likely that the inhibitory action of quinaprilat on ACE is necessary for the protective effect of the drug against LPC-induced changes. We therefore examined the effects of enalapril (another ACE inhibitor with the weak inhibitory action on ACE) and enalaprilat (an active metabolite of enalapril with an inhibitory action on ACE) on the LPC-induced changes. Both enalapril and enalaprilat attenuated the LPC-induced Ca<SUP>2+</SUP>-overload, suggesting that the inhibitory action on ACE may not mainly contribute to the protective effect of ACE inhibitors against LPC-induced Ca<SUP>2+</SUP>-overload. This suggestion was supported by the fact that neither ACE (0.2 U/ml) nor angiotensin II (0.1 - 100 μM) increased [Ca<SUP>2+</SUP>]<SUB>i</SUB> in isolated cardiomyocytes. Furthermore, application of bradykinin (0.01 - 10 μM) did not enhance the protective effect of quinaprilat against LPC-induced changes. LPC also increased release of creatine kinase (CK) from the myocyte markedly, and quinaprilat but not quinapril attenuated the LPC-induced CK release. Unexpectedly, both enalapril and enalaprilat did not attenuate the LPC-induced CK release. Neither quinapril nor quinaprilat changed the critical micelle concentration of LPC, suggesting that these drugs do not directly bind to LPC. We conclude that quinaprilat attenuates the LPC-induced increase in [Ca<SUP>2+</SUP>]<SUB>i</SUB>, and that the protective effect of quinaprilat on the LPC-induced change may not be related to a decrease in angiotensin II production or an increase in bradykinin production.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 79(1), 17-24, 1999-01

    The Japanese Pharmacological Society

References:  32

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008193996
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4636847
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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