The effects of angiotensin II (AII) on the antitumor activity and cardiotoxicity of doxorubicin (DXR) were tested in rats bearing Walker 256/A carcinoma. The animals received 2, 4 or 6 mg/kg of DXR as a bolus i.v. injection, with or without a concurrent i.v. infusion of 2 micrograms/kg/min of AII, starting 1 h prior to DXR administration for a total of 6 h. Neither the antitumor activity, nor the myocardial toxicity of DXR, as assessed by ECG evaluation (Q alpha T duration), were affected by AII at the tested dose. 100% of the animals receiving 6 mg/kg of DXR with or without AII were cured from the tumor, but subsequently some of them developed toxic signs and eventually died within the 12th week after treatment. Rats receiving DXR + AII showed a higher long-term survival than those receiving DXR alone; therefore, a possible interference with other DXR-induced side effects, such as nephrotoxicity, is hypothesized.
Effect of angiotensin II on the antitumor activity and cardiotoxicity of doxorubicin.
MONTI, ELENA CATERINA;PARACCHINI, LUISA;
1990-01-01
Abstract
The effects of angiotensin II (AII) on the antitumor activity and cardiotoxicity of doxorubicin (DXR) were tested in rats bearing Walker 256/A carcinoma. The animals received 2, 4 or 6 mg/kg of DXR as a bolus i.v. injection, with or without a concurrent i.v. infusion of 2 micrograms/kg/min of AII, starting 1 h prior to DXR administration for a total of 6 h. Neither the antitumor activity, nor the myocardial toxicity of DXR, as assessed by ECG evaluation (Q alpha T duration), were affected by AII at the tested dose. 100% of the animals receiving 6 mg/kg of DXR with or without AII were cured from the tumor, but subsequently some of them developed toxic signs and eventually died within the 12th week after treatment. Rats receiving DXR + AII showed a higher long-term survival than those receiving DXR alone; therefore, a possible interference with other DXR-induced side effects, such as nephrotoxicity, is hypothesized.
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