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Vasoactivity of trimetazidine on guinea‐pig isolated ductus arteriosus
Author(s) -
Garnier D.,
Roulet M.J.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb12936.x
Subject(s) - trimetazidine , ductus arteriosus , guinea pig , medicine , cardiology , pharmacology
1 The effect of trimetazidine (TMZ), an anti‐anginal drug, on the mechanical response of the guinea‐pig ductus arteriosus placed under conditions of mild hypoxia ( PO 2 ≅ 75 mmHg) was investigated. 2 When the PO 2 of the bathing solution was 75 mmHg, TMZ caused a dose‐dependent increase in tension. The median effective dose (ED 50 ) for the drug was 8 × 10 −5 m . 3 TMZ‐induced increase in tension was not significantly affected by pretreatment of the preparation with adrenoceptor blocking agents, or indomethacin. 4 The amplitude of the PO 2 ‐dependent tension was significantly augmented by exposure of the strip to TMZ 10 −4 m , whereas neither the resting tone (low PO 2 ), nor the oxygen‐induced contraction (high PO 2 ) were altered. 5 This ability of TMZ to increase the tension response during hypoxia was dependent on the external calcium concentration. 6 Under low PO 2 conditions, a contractile activity of 10 −4 m TMZ was unmasked in preparations perfused with 18 m m K + ‐PSS medium. This response to TMZ disappeared after the removal of calcium from the bath. 7 At the maximally effective dose of 10 −3 m , and during low PO 2 , the TMZ‐induced contractile response changed to a relaxation response when the external K + concentration was raised more than five fold. 8 The possibility that TMZ stimulates the mechanism by which oxygen normally controls the concentration of free intracellular calcium in the ductus arteriosus is proposed.