Abstract

This study evaluated the effects of voluntary ethanol consumption combined with testosterone treatment on cardiovascular function in rats. Moreover, we investigated the influence of exercise training on these effects. To this end, male rats were submitted to low-intensity training on a treadmill or kept sedentary while concurrently being treated with ethanol for 6 weeks. For voluntary ethanol intake, rats were given access to two bottles, one containing ethanol and other containing water, three 24-hour sessions per week. In the last two weeks (weeks 5 and 6), animals underwent testosterone treatment concurrently with exercise training and exposure to ethanol. Ethanol consumption was not affected by either testosterone treatment or exercise training. Also, drug treatments did not influence the treadmill performance improvement evoked by training. However, testosterone alone, but not in combination with ethanol, reduced resting heart rate. Moreover, combined treatment with testosterone and ethanol reduced the pressor response to the selective α1-adrenoceptor agonist phenylephrine. Treatment with either testosterone or ethanol alone also affected baroreflex activity and enhanced depressor response to acetylcholine, but these effects were inhibited when drugs were coadministrated. Exercise training restored most cardiovascular effects evoked by drug treatments. Furthermore, both drugs administrated alone increased pressor response to phenylephrine in trained animals. Also, drug treatments inhibited the beneficial effects of training on baroreflex function. In conclusion, the present results suggest a potential interaction between toxic effects of testosterone and ethanol on cardiovascular function. Data also indicate that exercise training is an important factor influencing the effects of these substances.

Highlights

  • Mental and substance use disorders are among major contributors to the burden of disease in the world [1]

  • Analysis of ethanol intake before the onset of testosterone treatment indicated an effect over time (F(5,202) = 3, P

  • Analysis of heart rate (HR) indicated a main effect of drug treatments (F(3,59) = 8, P0.05) and treatment x training interaction (F(3,59) = 0.6, P>0.05) (Fig 4)

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Summary

Introduction

Mental and substance use disorders are among major contributors to the burden of disease in the world [1]. Clinical and preclinical studies have demonstrated that alterations in contractile/relaxant properties of the vascular smooth muscle, changes in neuroendocrine function, impairment of baroreflex activity, and autonomic unbalance constitute important mechanisms underlying the negative cardiovascular effects of heavy ethanol consumption [3,4,6,7,8]. Clinical evidence indicated that abuse of androgenic—anabolic steroids (AASs) was positively associated with ethanol use and dependence [14,15,16]. These findings are corroborated by preclinical studies showing that AAS can affect voluntary ethanol consumption and ethanol preference [17,18,19]. Despite the evidence that AAS and ethanol are co-abused, the potential toxic effects of the concomitant use of these substances are unknown

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