Lisinopril increases the recovery during reoxygenation and resistance to oxidative damage in cardiomyocytes.
The action of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the consequences of myocardial reoxygenation and oxidative damage was assessed in cultured chick embryonic ventricular cardiomyocytes. Lisinopril, 10(-8) M to 10(-6) M, produced a significant (P < 0.05) dose-dependent enhancement of the restoration of contractile frequency occurring during myocardial reoxygenation but did not alter the depression in contractile frequency during hypoxia. Lisinopril significantly (P < 0.05) shifted the dose-response relationship of ammonium persulfate-induced reduction in cardiac contractile frequency. Lisinopril significantly (P < 0.05) reduced the effect of another oxidative agent, tertbutylhydroperoxide which produced a time-dependent reduction in cardiac contractile frequency. Lisinopril did not alter cardiac contractile frequency in the absence of hypoxia or ammonium persulfate or tertbutylhydroperoxide. The viability of cardiomyocytes, assessed by trypan blue exclusion, paralleled the changes in cardiac contractile frequency. Lisinopril significantly (P < 0.05) improved viability of cardiomyocytes exposed to either ammonium persulfate or tertbutylhydroperoxide. Lisinopril did not display any antioxidant properties against the free radical alpha,alpha-diphenyl-beta-picrylhydrazyl. These data suggest that lisinopril accelerates the recovery of cardiomyocytes during reoxygenation and blunts the effects of oxidative agents through mechanisms involving the endogenous renin angiotensin system and/or a direct cellular action.
Rabkin
S W
SW
University of British Columbia, Vancouver, Canada.
D000645:Ammonium Sulfate / Q000633:toxicity; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D017706:Lisinopril / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D010545:Peroxides / Q000633:toxicity; D020122:tert-Butylhydroperoxide
D000806:Angiotensin-Converting Enzyme Inhibitors; D016877:Oxidants; D010545:Peroxides; C031276:ammonium peroxydisulfate; D020122:tert-Butylhydroperoxide; D017706:Lisinopril; D000645:Ammonium Sulfate