Cardiovascular Toxicology

, Volume 5, Issue 4, pp 377–389 | Cite as

Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling

  • Frank A. LattanzioJr.
  • David Tiangco
  • Christopher Osgood
  • Stephen Beebe
  • Julie Kerry
  • Barbara Y. Hargrave
Original Research

Abstract

To determine the cardiovascular molecular events associated with acute exposure to cocaine, the present study utilized in vivo analysis of left-ventricular heart function in adult rabbits fluorescence confocal microscopy of fluo-2, rhod-2, (5-(and-6) carboxy 2′, 7′ dichlorodihydrofluores-cein diacetate (carboxy-H2DCFDA), and JC-1 in H9C2 cells and gene expression microarray technology for analysis of gene activation in both rabbit ventricular tissue and H9C2 cells. In the rabbit, acute cocaine exposure (2 mg/kg) caused left-ventricular dysfunction and 0.1–10 mM cocaine increased cytosolic and mitochondrial calcium activity and mitochondrial membrane depolarization in H9C2 cells. A 3-min pretreatment of H9C2 cells by 10 μM verapamil, nifedipine, or nadolol inhibited calcium increases, but only 1 mM N-acetylcysteine (NAC) or 1 mM glutathione blocked mitochondrial membrane depolarization. Cocaine induced activation of genes in the rabbit heart and H9C2 cells including angiotensinogen, ADRB1, and c-reactive protein (CRP). In H9C2 cells NAC pretreatment blocked cocaine-mediated increases in CRP, FAS, FAS ligand, and cytokine receptor-like factor 1 (CRLF1) expression. Collectively, these data suggest that acute cocaine administration initiates cellular and genetic changes that, if chronically manifested, could cause cardiac deficits similar to those seen in heart failure and ischemia, such as ventricular dysfunction, cardiac arrhythmias, and cardiac remodeling.

Keywords

Cocaine Nifedipine Brain Natriuretic Peptide Atrial Natriuretic Peptide H9C2 Cell 

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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Frank A. LattanzioJr.
    • 1
  • David Tiangco
    • 2
  • Christopher Osgood
    • 2
  • Stephen Beebe
    • 1
  • Julie Kerry
    • 1
  • Barbara Y. Hargrave
    • 2
  1. 1.Department of Physiological SciencesEastern Virginia Medical SchoolNorfolk
  2. 2.Dept. of Biological SciencesOld Dominion University, Hampton Blvd.Norfolk

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