MOLECULAR CHARACTERISTICS OF COCAINE-INDUCED CARDIOMYOPATHY IN RATS

Cocaine abuse induces severe cardiomyopathy. To investigate the molecu lar effects of acute and prolonged administration of cocaine, mRNAs en coding markers of either mechanical overload, as atrial natriuretic fa ctor (ANF) and alpha- and beta-myosin heavy chains, or fibrosis as typ e I and III procollagens, were quantitated in the left ventricle of ra ts 4 h after one injection of cocaine (40 mg/kg, n = 7), or 14 (n = 15 ) and 28 days (n = 10) after chronic infusion of cocaine (40 mg/kg per day). Plasma cocaine and benzylecgonine concentrations were both sign ificantly augmented during the infusion while plasma levels of triiodo thyronine and thyroxin-were lowered. Acute injection of cocaine induce d ANF gene expression. Cocaine treatment during 28 days resulted in le ft ventricular hypertrophy (+ 20% after 24 days, P < 0.05) with normal blood pressure, associated with an accumulation of mRNAs encoding ANF and type I and III collagens (+66% and +55%, P < 0.05). Such a chroni c treatment also induced a shift from the cu-to the P-myosin heavy cha in gene expression (-40% and +50%, P < 0.05). In conclusion, cocaine a ctivates markers of both hemodynamic overload and fibrosis. Such an ac tivation may result from direct and/or indirect effects of the drug su ch as myocardial ischemia, mechanical overload and/or hypothyroidism. (C) 1997 Elsevier Science B.V.