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Cardiovascular Research 2005 67(4):699-704; doi:10.1016/j.cardiores.2005.04.026
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Copyright © 2005, European Society of Cardiology

Role of {alpha}1-adrenoreceptors in cocaine-induced NADPH oxidase expression and cardiac dysfunction

Marc Isabelle, Christelle Monteil*, Fabienne Moritz, Brigitte Dautreaux, Jean-Paul Henry, Vincent Richard, Paul Mulder and Christian Thuillez

INSERM U644, Faculté de médecine-Pharmacie de Rouen, UFR de Medecine et de Pharmacie, 22 boulevard Gambetta, 76183 Rouen, France

* Corresponding author. Tel.: +33 2 35 14 84 75; fax: +33 2 35 14 83 65. Email address: christelle.monteil{at}univ-rouen.fr

Objective: We assessed whether {alpha}1-adrenoreceptor ({alpha}1-AR) stimulation contributes to activation of myocardial NADPH oxidase in a rat model of cocaine-induced cardiac dysfunction.

Methods and results: After 7 days of cocaine injection (2 x 7.5 mg/kg/day, i.p., Coc), NADPH activity assessed by chemiluminescence increases as well as phosphorylation of p47phox, one of the cytosolic components of NADPH oxidase. The {alpha}1-AR antagonist prazosin (Prz), administered 1 h before each cocaine injection (2 x 1 mg/kg/day, i.p., Coc+Prz), prevents these effects. Moreover, Prz pretreatment reduces left ventricular/body weight (LV/BW) ratio and partially prevents the cocaine-induced alterations in fractional shortening and cardiac index assessed by echocardiography. In order to confirm the involvement of {alpha}1-AR stimulation in NADPH oxidase up-regulation in vivo, we used phenylephrine (Phe) administration with the same protocol of injections as that used with cocaine (2 x 5 µg/kg/day, i.p.). After Phe administration, as expected, NADPH oxidase activity increases as well as phosphorylation of p47phox. These effects occur in the absence of sustained hemodynamic changes.

Conclusion: This study demonstrates the involvement of the {alpha}1-AR in NADPH oxidase activation and in cocaine-induced LV dysfunction. We suggest that {alpha}1-AR stimulation, at least in part via NADPH oxidase induction, plays a critical role in the events leading to the cardiomyopathy observed after cocaine abuse.

KEYWORDS {alpha}1-Adrenoreceptor; Cocaine; Free radicals; Ventricular function; Superoxide; Hypertrophy

Time for primary review 23 days


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