264 Effects of Angiotensin-1 Converting Enzyme inhibition on oxidative stress and bradykinin receptor expression during doxorubic in-induced cardiomyopathy in rats

Abstract

To evaluate the mechanisms and the impact of the ACE-inhibitor perindopril (P) in a model of doxorubicin (D)- induced cardiotoxicity, male Wistar rats received D (1mg/kg/d, i.p. 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, 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 cTnI, BNP 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 modulated kinin receptor expression and enhanced antioxidant defense.