Baroreflex sensitivity and oxidative stress in adriamycin-induced heart failure.

Abstract

Adriamycin cardiotoxicity is associated with oxidative stress in the presence of globally depressed cardiac function. It is unknown if there is a similar profile with early diastolic changes and how it relates to baroreflex control of circulation. In this study, we evaluated baroreflex control of circulation in adriamycin-treated Wistar rats compared with controls, using invasive blood pressure recording processed by a data acquisition system (CODAS, 1 KHz). Baroreflex sensitivity was evaluated by modulating blood pressure with phenylephrine and sodium nitroprusside. Oxidative stress was quantified by chemiluminescence and by glutathione peroxidase enzyme activity. Diastolic dysfunction was characterized by increased left ventricle end-diastolic pressure in adriamycin-treated rats compared with controls with preserved ascending aortic flow. Baroreflex sensitivity in response to blood pressure elevation and reduction were similar in adriamycin (-2+/-0.27 and -3.19+/-0.56 bpm/mm Hg) and control rats (-1.35+/-0.15 and -2.52+/-0.39 bpm/mm Hg). Chemiluminescence was higher (20450+/-1286 versus 16517+/-1020 counts per second/mg protein) and glutathione peroxidase activity was lower (45.6+/-4.3 versus 76.4+/-6.9 micromol. min(-1). mg(-1) protein) in adriamycin rats compared with controls. Inverse correlations were observed between glutathione peroxidase activity and left ventricle end-diastolic pressure (r=-0.72, P=0.02), between baroreflex sensitivity to phenylephrine and left ventricle end-diastolic pressure (r=-0.77, P=0.004), and between chemiluminescence and baroreflex sensitivity to sodium nitroprusside (r=-0.75, P=0.02), whereas a positive correlation was observed between baroreflex sensitivity to sodium nitroprusside and glutathione peroxidase activity (r=0.7, P=0.04). Thus, adriamycin led to increased left ventricle end-diastolic pressure without changes in baroreflex sensitivity, and associated increased oxidative stress appeared to be related to reduction of reflex control of circulation.