Cilazapril and captopril accelerate recovery from hypoxia in myocardial cell aggregates in culture.
We wished to determine whether angiotensin-converting enzyme (ACE) inhibition alters the effect of hypoxia and reoxygenation directly on the cardiac myocyte; to compare two different ACE inhibitors, one with and one without a sulfhydryl group (i.e., captopril and cilazapril), and to examine the potential interaction of these ACE inhibitors with agents that purportedly prevent the deleterious action of oxygen-derived free radicals. Ventricular myocytes were obtained from 7-day-old chick embryo hearts and were maintained in culture for 96 h before study. Hypoxia produced a significant (p less than 0.05) and marked reduction in cardiac contractile frequency that was not influenced by captopril 10(-6) and 10(-7) M or cilazapril 10(-6) or 10(-7) M. During the reoxygenation period, cardiac contractile frequency gradually returned to normal. Both ACE inhibitors, captopril and cilazapril, were associated with a similar significant (p less than 0.05) enhancement of restoration of contractile frequency. Angiotensin II (ANGII) reversed the effect of these ACE inhibitors. Two agents that reduce reoxygenation-induced myocardial damage, perhaps through alteration in production or degradation of oxygen-derived free radicals, i.e., allopurinol and superoxide dismutase (SOD), significantly (p less than 0.05) accelerated recovery of cardiac myocytes during reoxygenation. There was no additive effect with either captopril or cilazapril plus allopurinol or SOD. Conclusions about the actions of these ACE inhibitors must be tempered by the evidence that substrates other than ANGI, particularly bradykinin, are processed by the enzyme and inhibited by ACE inhibitors so that some of the observed effects may have been due to accumulation of other substrates.(ABSTRACT TRUNCATED AT 250 WORDS)
Rabkin
S W
SW
Cardiovascular Research Laboratories, University Hospital Shaughnessy, University of British Columbia, Vancouver, Canada.
D000493:Allopurinol / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D017315:Cilazapril; D005609:Free Radicals / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D010100:Oxygen / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D005609:Free Radicals; D011724:Pyridazines; D017315:Cilazapril; D000493:Allopurinol; D002216:Captopril; D010100:Oxygen