Open AccessEffects of Angiotensin-1 Converting Enzyme Inhibition on Oxidative Stress and Bradykinin Receptor Expression During Doxorubicin-induced Cardiomyopathy in Rats
Author(s) -
Carole Richard,
Benjamin Lauzier,
Stéphanie Delemasure,
Sébastien Talbot,
Stéliana Ghibu,
Bertrand Collin,
Jacques Sénécal,
Franck Ménétrier,
Catherine Vergely,
Réjean Couture,
Luc Rochette
Publication year - 2008
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/fjc.0b013e3181865f28
Subject(s) - endocrinology , kinin , medicine , oxidative stress , perindopril , bradykinin , angiotensin converting enzyme , cardiotoxicity , receptor , chemistry , antioxidant , blood pressure , chemotherapy , biochemistry
To evaluate the mechanisms and the impact of the angiotensin-converting enzyme inhibitor perindopril (P) in a model of doxorubicin (D)-induced cardiotoxicity, male Wistar rats received D (1 mg/kg/d, IP for 10 days), P (2 mg/kg/d by gavage from day 1 to day 18), D (for 10 days) + P (for 18 days) or saline. D decreased systolic blood pressure and body and heart weights. Left ventricular diastolic diameter was increased by D (P < 0.01), but it was not attenuated by P. D decreased plasma vitamin C (P < 0.05) and increased the ascorbyl radical/vitamin C ratio (P < 0.01). This ratio was attenuated by P. No difference was found among groups in cardiac troponin I, brain natriuretic peptide concentrations, and tissue oxidative stress (OS). Myocardial MCP-1 expression was higher in the D group. Cardiac kinin receptor (B1R and B2R) expression was not affected by D, yet binding sites for B2R and B1R were increased in D+P and P groups, respectively (P < 0.05). In conclusion, D induced cardiac functional alterations, inflammation and plasma OS whereas tissue OS, and cardiac kinin receptors expression were not modified. P did not improve cardiac performance, but it modulated kinin receptor expression and enhanced antioxidant defense.