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AN ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR PROTECTS AGAINST DOXORUBICIN‐INDUCED IMPAIRMENT OF CALCIUM HANDLING IN NEONATAL RAT CARDIAC MYOCYTES
Author(s) -
Maeda Atsuyoshi,
Honda Masaaki,
Kuramochi Takehiko,
Tanaka Koichi,
Takabatake Toshikazu
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb02119.x
Subject(s) - angiotensin converting enzyme , myocyte , doxorubicin , calcium , pharmacology , enzyme , medicine , chemistry , endocrinology , chemotherapy , biochemistry , blood pressure
SUMMARY 1. The effects of doxorubicin (DOX) on intracellular calcium transients were examined in neonatal rat cultured cardiac myocytes, as were the cardioprotective effects of an angiotensin‐converting enzyme (ACE) inhibitor on DOX‐induced impairment of calcium handling. 2. Cultured cardiac myocytes isolated from neonatal Wistar‐Kyoto rats were treated with DOX for 24 h. Field‐stimulated calcium transients in single myocytes were measured in the presence or in the absence of isoproterenol using fura‐2/AM. Calcium transients were also measured after the addition of DOX to myocytes pretreated with M‐I (an active metabolite of delapril HC1, an ACE inhibitor. 3. Doxorubicin reduced the amplitude and maximum velocity of increase and decrease of calcium transients, prolonged the time‐course of calcium transients and impaired the β‐adrenoceptor responsiveness of calcium transients in a dose‐dependent manner. The DOX‐induced impairment of calcium transients and (5‐adrenoceptor responsiveness was improved by M‐I. 4. Doxorubicin impaired both the mobilization and sequestration of intracellular calcium ions in contraction‐relaxation cycles and the response of calcium transients to (3‐adrenocep‐tor stimulation. The ACE inhibitor ameliorated DOX‐induced impairment of calcium dynamics, suggesting that M‐I, an active metabolite of delapril, protects against DOX‐induced abnormal calcium handling leading to cardiac dysfunction.