title: Cocaine increases beta-myosin heavy-chain protein expression in cardiac myocytes.
abstract: BACKGROUND
  As many as 47% of chronic cocaine users develop cardiac ventricular hypertrophy. The presence and degree of cocaine-induced ventricular hypertrophy is not correlated with the use of other substances of abuse such as alcohol or cigarettes. Moreover, this hypertrophy occurs in individuals without sustained increases in arterial blood pressure or heart rate, or increases in the plasma concentration of renin, aldosterone, norepinephrine, or cortisol. Therefore, we investigated whether cocaine, in concentrations commonly found in cocaine users, has any direct effects on the protein content in cardiac ventricular myocytes. We compared the effects of cocaine with norepinephrine, which increases the total protein content, especially beta-myosin heavy-chain contractile protein (beta-MHC), in cardiac ventricular myocytes.
  
  
  METHODS
  Experiments were performed on 30-day-old rat ventricular myocytes suspended in culture media and cultured in flasks. In 12 suspension-culture experiments, cocaine or norepinephrine, in doses of 0 (control) or 10(-6) mol/L was added to each culture and the cells were harvested on day 5. In 16 flask-culture experiments, cocaine or norepinephrine was added to each culture on day 7 in doses of 0 (control-vehicle), 10(-7), or 10(-6) mol/L and the cells were harvested on day 10. The total protein content and the myosin protein expression of the myocytes in each culture were determined. Juvenile and adult rat cardiac myosin protein is predominately alpha-myosin heavy-chain protein (alpha-MHC), whereas beta-MHC occurs primarily in fetal rat hearts.
  
  
  RESULTS
  In the suspension-culture experiments, cocaine, 10(-6) mol/L, increased the cardiomyocyte total protein concentration by 29% +/- 2% (P <.001) and the beta-MHC expression by 81% +/- 10% (P <.01) in comparison with the control myocytes. Cocaine slightly decreased cardiomyocyte alpha-MHC. Norepinephrine increased the total protein concentration by 21% +/- 3% (P <.001) and the beta-MHC expression by 59% +/- 10% (P <.01), but did not increase alpha-MHC expression. In the flask-culture experiments, cocaine, 10(-6) mol/L, maximally increased the total protein concentration by 28% (P <.001), the protein/cell ratio by 57% +/- 10% (P <.01), and the beta-MHC expression by 85% +/- 8% (P <.01). Cocaine slightly decreased alpha-MHC. Norepinephrine, 10(-6) mol/L, maximally increased the total protein concentration by 35%, the protein/cell ratio by 63% +/- 9% (P <.01), and the expression of beta-MHC by 78% +/- 11% (P <. 01). Norepinephrine did not increase alpha-MHC expression. In 18 separate flask-culture experiments, cocaine, 10(-6) mol/L, was added to the cardiomyocyte cultures after the addition of phentolamine (n = 9), in concentrations of 10(-7) to 10(-5) mol/L, or metoprolol (n = 9), in concentrations of 10(-7) to 10(-5) mol/L. Neither phentolamine nor metoprolol inhibited the cocaine-induced increase in cardiomyocyte total protein content or the expression of beta-MHC.
  
  
  CONCLUSIONS
  Cocaine, similar to norepinephrine, significantly increases the total protein content and the expression of beta-MHC in cardiac ventricular myocytes. In this manner, cocaine may cause cardiac ventricular hypertrophy. This process is not inhibited by alpha- or beta-adrenergic receptor blockade.
authors.affiliation: University of South Florida College of Medicine, Tampa, FL 33612, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Henning
authors.forename: J
authors.initials: J
authors.lastname: Silva
authors.forename: V
authors.initials: V
authors.lastname: Reddy
authors.forename: S
authors.initials: S
authors.lastname: Kamat
authors.forename: M B
authors.initials: MB
authors.lastname: Morgan
authors.forename: Y X
authors.initials: YX
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Chiou
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000503:physiopathology; D018929:Cell Culture Techniques; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000166:cytology; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018765:Dopamine Uptake Inhibitors; D018995:Myosin Heavy Chains; D003042:Cocaine; D009638:Norepinephrine