Vasomotor responses in rats "intoxicated" with doxorubicin

In rats intoxicated with doxorubicin, vasomotor responses were evaluated 12 hr after the last dosage. In rats pretreated with doxorubicin, hypertensive responses to L-norepinephrine and L-epinephrine, and hypertension by occlusion of both common carotid arteries were significantly (p < 0.05) reduced when compared with controls. Doxorubicin pretreatment also significantly reduced the arterial hypotension due to L-isoprenaline. In rats intoxicated with doxorubicin, pretreatment with L-sulpiride (12.5 to 50 mg/Kg/day for 30 days in drinking water ad libitum) did not modify the effects of doxorubicin on vasomotor reactivity. In contrast, pretreatment with amitriptyline (12.5 to 50 mg/Kg/day in drinking water ad libitum for 30 days) potentiated the inhibitory effects of doxorubicin on vasomotor responses. In conclusion, our research shows that doxorubicin intoxication induces a significant reduction of alpha- and beta-adrenergic reactivity and of baroreceptor activity.