We examined the effects of the
angiotensin converting enzyme (
ACE) inhibitors captopril,
enalaprilat,
quinapril, and
trandolapril, and their active metabolites
quinaprilat and
trandolaprilat, on
hemolysis induced by
lysophosphatidylcholine (LPC) in human erythrocytes. LPC induced
hemolysis at the concentrations above the critical
micelle concentration (4 microM).
Propranolol, used as a reference
drug, attenuated the 50%
hemolysis induced by 6 microM LPC at concentrations ranging from 100 nM to 100 microM. Similarly,
quinaprilat (10 microM) and
trandolaprilat (10, 100 microM) significantly attenuated the LPC-induced
hemolysis, but other
ACE inhibitors did not. Since
propranolol possesses a membrane stabilizing action correlated with high lipophilicity, it appears that the high lipophilicity of
quinaprilat or
trandolaprilat is responsible for the protection from the damage induced by LPC. However,
quinapril and
trandolapril were not effective, although both drugs have higher lipophilicity than
quinaprilat and
trandolaprilat. Hence, it is suggested that the high lipophilicity alone may not contribute to the protective effects of
ACE inhibitors against LPC-induced
hemolysis. None of
ACE inhibitors attenuated the hypotonic
hemolysis (60 mM NaCl), although
propranolol did. Furthermore, neither
propranolol (100 microM) nor
quinaprilat (50 microM) and
trandolaprilat (50 microM) affected LPC
micelle formation, suggesting that these drugs do not directly bind to LPC. We therefore believe that the protective effects of
quinaprilat and
trandolaprilat on the LPC-induced
hemolysis may be related physicochemically to their highly lipophilic and ACE inhibitory structures, which probably maintain erythrocyte membrane integrity by a mechanism other than ACE inhibition, prevention of LPC
micelle formation or protection against osmotic imbalance.