Protective effects of quinaprilat and trandolaprilat, active metabolites of quinapril and trandolapril, on hemolysis induced by lysophosphatidylcholine in human erythrocytes.
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.
Hayase
Nobumasa
N
Departments of Hospital Pharmacy & Pharmacology, Asahikawa Medical College, Hokkaido, Japan. nh2767@asahikawa-med.ac.jp
Satomi
Machiko
M
Hara
Akiyoshi
A
Awaya
Toshio
T
Shimizu
Keiko
K
Matsubara
Kazuo
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism* / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000633:toxicity*; D008823:Micelles; D011433:Propranolol / Q000494:pharmacology; D000077583:Quinapril; D012965:Sodium Chloride / Q000494:pharmacology; D044005:Tetrahydroisoquinolines / Q000378:metabolism* / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007038:Hypotonic Solutions; D007211:Indoles; D008244:Lysophosphatidylcholines; D008823:Micelles; D044005:Tetrahydroisoquinolines; C052035:trandolapril; C054501:quinaprilat; D012965:Sodium Chloride; D011433:Propranolol; D000077583:Quinapril; C061095:trandolaprilat