Doxorubicin cardiotoxicity is associated with alterations of plasma levels of atrial natriuretic factor.
In order to determine the involvement of the atrial natriuretic factor (ANF) in a model of drug-induced cardiomyopathy, the effects of a single or repeated doses of doxorubicin on plasma ANF levels were examined. Female Wistar rats were treated with doxorubicin at two different schedules: a single 10 mg/kg iv dose or multiple 3 mg/kg iv doses once a week for 3 weeks; control groups were given vehicle (isotonic saline, 0.9% NaCl) intravenously. ANF was assayed in plasma by a specific and sensitive radioimmunoassay method and cardiac function was evaluated by monitoring of ECG and hemodynamic parameters. In the doxorubicin single-dose study plasma ANF values were measured during a period of 6 hours after dosing and were found to be significantly decreased at the 180th (12.5 +/- 2.9 pg/ml) and 360th minute (19.4 +/- 1.2 pg/ml) after dosing, compared to vehicle-treated animals (35.1 +/- 5.7 and 37.9 +/- 4.1 pg/ml, 180 and 360th minute, respectively). Rats treated with multiple doses of doxorubicin showed a significant increase in plasma ANF levels at the 21st (88.3 +/- 7.7 pg/ml) and 31st day (61.0 +/- 14.3 pg/ml) of the study compared to vehicle-treated animals at the same time points (41.8 +/- 8.0 and 26.5 +/- 7.2 pg/ml, respectively). At the 42nd day plasma ANF concentration in doxorubicin-treated rats was not significantly different from vehicle-treated rats. In both studies ANF level changes occurred in the setting of acute or chronic doxorubicin-induced cardiac damage, as evidenced by alterations of hemodynamic and ECG parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
Bernardini
N
N
Istituto di Farmacologia Medica, Università di Pisa, Italy.
Agen
C
C
Favilla
S
S
Danesi
R
R
Del Tacca
M
M
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D009202:Cardiomyopathies / Q000097:blood* / Q000139:chemically induced; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains
D004317:Doxorubicin; D009320:Atrial Natriuretic Factor