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.
Filippelli
W
W
Institute of Pharmacology and Toxicology, First Faculty of Medicine and Surgery, University of Naples Federico II, Italy.
Russo
S
S
Marrazzo
R
R
Marmo
M
M
Rossi
F
F
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D004357:Drug Synergism; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D013469:Sulpiride / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects*
D000639:Amitriptyline; D013469:Sulpiride; D004317:Doxorubicin; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine