ORIGINAL ARTICLE Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreﬂex Activity in Unanesthetized Rats Sheila A. Engi, BS,*† Fábio C. Cruz, PhD,* Rodrigo M. Leão, BS,*† Fernando M. Corrêa, PhD,‡ Cleopatra S. Planeta, PhD,*† and Carlos C. Crestani, PhD*† Abstract: Abuse of cocaine and androgenic–anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic–anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testoster- one and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreﬂex activity, and hemodynamic responses to vasoac- tive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreﬂex activity and impairment of both hypotensive response to intravenous sodium nitro- prusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreﬂex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreﬂex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or com- bined administration of the drugs did not affect any parameter investi- gated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined adminis- tration of these 2 drugs may result from alterations in baroreﬂex activity and impairment of vascular responsiveness to vasoactive agents. Key Words: abuse, anabolic steroids, cocaine, cardiovascular, hypertension, hypertrophy, vascular reactivity (J Cardiovasc Pharmacol Ô 2012;59:231–240) INTRODUCTION Abuse of cocaine and androgenic–anabolic steroids (AAS) abuse become a serious public health problem. 1–3 Emerging data indicate that AAS use is associated with abuse of psychotropic drug. 4 Indeed, some results have pointed that cocaine is the drug most frequently coabused by AAS users. 5,6 These data are alarming because although many reports have documented the side effects of single AAS or cocaine abuse, a limited number of studies have assessed the potential toxic effects of the concomitant use of these substances. The widespread abuse of cocaine and AAS has stimulated interest in the toxic effects of these drugs. 7,8 Both cocaine and AAS abuse have been related to cardiovascular complications. 9,10 Cocaine use has been associated with acute and chronic cardiovascular toxicity. 7,10 Acute admin- istration of cocaine evokes a range of cardiovascular effects including hypertension, coronary vasoconstriction, and car- diac arrhythmias. 7,10 However, cardiovascular consequences of chronic cocaine abuse are less understood. 7,10 This is an important issue, because it has been proposed that cardio- vascular complications are mainly because of chronic use of cocaine. 10,11 Unlike cocaine, AAS evokes minor acute cardiovascular side effects. 8 However, chronic AAS abuse has been associated with hypertension and cardiac pathologies. 8,9 Moreover, studies in animals have proposed that AAS and cocaine are capable of mutually potentiating the cardiovascular effects of each other, 12–14 thus suggesting a potential interaction between toxic effects of these drugs on cardiovascular function. Although the above studies describe cardiovascular diseases after either single or com- bined use of cocaine and AAS, the mechanisms involved in the physiopathological process of these complications are not clear. Impairment of baroreﬂex activity has been proposed to contribute to the pathogenesis of a number of cardio- vascular diseases, such as hypertension, heart failure, and myocardial infarction. 15,16 Consequently, cardiovascular complications after cocaine and/or AAS administration may be associated with changes in baroreﬂex activity. Indeed, it has been reported that treatment for 8 weeks with the AAS stanozolol evoked hypertension in rats, which was associated with changes in cardiac baroreﬂex activity. 17 Although acute administration of cocaine inhibits baroreﬂex activity in rats, 18 the effect of chronic Received for publication August 15, 2011; accepted October 12, 2011. From the *Laboratory of Pharmacology, Department of Natural Active Princi- ples and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, UNESP, Araraquara, Brazil; †Joint UFSCar-UNESP Graduate Program in Physiological Sciences, Araraquara-SP and São Carlos-SP, Brazil; and ‡Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. Supported by grants from the Fundação de Amparo a Pesquisa do Estado de São Paulo (2010/16192-8), Conselho Nacional de Desenvolvimento Cientíﬁco e Tecnológico (474177/2010-6), Programa de Apoio ao Desen- volvimento Cientíﬁco da Faculdade de Ciências Farmacêuticas, and Fun- dação para Desenvolvimento da UNESP. Reprints: Carlos C. Crestani, PhD, Laboratory of Pharmacology, Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, UNESP, Rodovia Araraquara-Jau Km 01 (Campus Universitário), 14801-902, Caixa Postal 502, Araraquara, SP, Brazil (e-mail: cccrestani@yahoo.com.br). Copyright © 2012 by Lippincott Williams & Wilkins J Cardiovasc Pharmacol ä  Volume 59, Number 3, March 2012 www.jcvp.org | 231