Effects of angiotensin-1 converting enzyme inhibition on oxidative stress and bradykinin receptor expression during doxorubicin-induced cardiomyopathy in rats.
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.
Richard
Carole
C
Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaires Expérimentales, IFR 100, Facultés de Médecine et Pharmacie, Dijon cedex, France. carolealinerichard@yahoo.fr
Lauzier
Benjamin
B
Delemasure
Stéphanie
S
Talbot
Sébastien
S
Ghibu
Stéliana
S
Collin
Bertrand
B
Sénécal
Jacques
J
Menetrier
Franck
F
Vergely
Catherine
C
Couture
Réjean
R
Rochette
Luc
L
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001205:Ascorbic Acid / Q000097:blood; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy*; D018932:Chemokine CCL2 / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020913:Perindopril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000187:drug effects / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000187:drug effects / Q000378:metabolism; D019210:Troponin I / Q000187:drug effects / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000903:Antibiotics, Antineoplastic; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D019210:Troponin I; D020097:Natriuretic Peptide, Brain; D004317:Doxorubicin; D001205:Ascorbic Acid; D020913:Perindopril