Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

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 testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive 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 nitroprusside 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 combined administration of the drugs did not affect any parameter investigated. 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 administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.

Cardiovascular and autonomic alterations in rats with Parkinsonism induced by 6-OHDA and treated with L-DOPA

“…The direct recording of BP and HR was conducted using the implanted arterial cannula in the femoral artery in accordance with previous work ( [23,50,51,10]). The recording was done while the animals were awake and freely moving.…”

Cardiovascular Complications following Chronic Treatment with Cocaine and Testosterone in Adolescent Rats

“…Cocaine’s acute effects on cardiovascular function are well described and include hypertension, coronary vasoconstriction and cardiac arrhythmias [10], [13]. Cardiovascular toxicity following chronic cocaine exposure is less understood, but clinical and preclinical studies have reported myocarditis, arrhythmias, alterations in baroreflex activity, and vascular dysfunctions [10], [14]. Studies in humans and animals have also associated chronic AAS administration with cardiovascular complications, including hypertension, atherosclerosis, cardiac pathologies, impairment of baroreflex activity and changes in vascular function [12], [14]–[16].…”

“…Cardiovascular toxicity following chronic cocaine exposure is less understood, but clinical and preclinical studies have reported myocarditis, arrhythmias, alterations in baroreflex activity, and vascular dysfunctions [10], [14]. Studies in humans and animals have also associated chronic AAS administration with cardiovascular complications, including hypertension, atherosclerosis, cardiac pathologies, impairment of baroreflex activity and changes in vascular function [12], [14]–[16]. Interestingly, preclinical studies have demonstrated that concomitant AAS and cocaine treatment potentiate the cardiovascular effects of each other [17]–[19].…”

Efeitos do estresse crônico sobre as respostas cardiovasculares e ventilatórias ativadas pelo quimiorreflexo e barorreflexo em ratos

“…Segundo Engi et al,(2012) o prejuízo da atividade do barorreflexo pode contribuir para a patogênese de várias doenças cardiovasculares. Nesse contexto, a reversão eficiente de mudanças autonômicas provocadas pelo estresse é importante para reduzir as chances de patologias que em longo prazo podem induzir alterações cardiovasculares (Crestani et al, 2010c).…”

“…Vários estudos na literatura demonstram que uma das formas de avaliar a sensibilidade barorreflexa é através da quantificação da resposta reflexa de FC frente às variações de PA desencadeadas por drogas vasoativas (Crestani et al, 2006, Resstel et al, 2006b, Crestani et al, 2010a, Engi et al, 2012. No entanto, neste estudo a sensibilidade do barorreflexo também foi avaliada no domínio do tempo por meio do método da sequência.…”