Comparison of acute effects of mitoxantrone and doxorubicin in guinea-pig atria.
1. The acute effects of doxorubicin (DOX) and mitoxantrone (MTX) on basal rate and on positive chronotropic activity induced by 1-noradrenaline (1-NA) were investigated in isolated guinea-pig atria. 2. DOX (10(-5)-10(-4)M) progressively depressed atrial rate after a short latency period. Only 10(-4) M MTX reduced the spontaneous frequency after 120 and 180 min incubation. This effect was significantly lower to that elicited by DOX (10(-4)M). 3. Atropine (1.5 x 10(-6) M) and reserpine pretreatment did not affect the negative chronotropic action induced by DOX or MTX. 4. DOX (10(-5)-10(-4) M) produced a significant reduction of the maximal chronotropic response (Emax) to 1-noradrenaline (1-NA) after 60, 120 and 180 min of exposure. 5. MTX (10(-5)-10(-4) M) after 60 and 120 min incubation induced a beta-adrenergic, concentration- and time-dependent, competitive blocking effect. After 180 min of exposure, MTX (10(-4) M) reduced the Emax to 1-NA which was of less magnitude to that produced by DOX (10(-4) M). 6. Although both DOX and MTX depressed spontaneous and 1-NA induced chronotropic activity, MTX effects were of a slower onset and development compared to those exerted by DOX.
Viglione
P N
PN
Departamento de Fisiologia, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Praprotnik
A
A
Politi
P M
PM
Pinto
J E
JE
D000818:Animals; D016275:Atrial Function; D001285:Atropine / Q000494:pharmacology; D003864:Depression, Chemical; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013268:Stimulation, Chemical
D001285:Atropine; D004317:Doxorubicin; D012110:Reserpine; D008942:Mitoxantrone; D009638:Norepinephrine