Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by β-adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non-treated (Con); sedentary isoprenaline treated (Iso); exercised non-treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real-time RT-PCR and Western blot were used to quantify tumour necrosis factor α, interleukin-6, interleukin-10 and transforming growth factor β 1 (TGF-β 1 ) in the tissue. NF-κB expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of tumour necrosis factor α and interleukin-6, as well as TGF-β 1 mRNA, were increased. In addition, the NF-κB expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin-10 levels; and (4) it attenuated the increase of TGF-β 1 mRNA. Thus, exercise training in a model of β-adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance. Abbreviations CSA, cross-sectional area; +dP/dt, maximal positive time derivate of the developed pressure; −dP/dt, maximal negative time derivate of the developed pressure; DT, developed tension; +dT/dt, maximal rate of tension increase; −dT/dt, maximal rate of tension decrease; FS, left vetricular fractional shortening; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HR, heart rate; IL-6, interleukin-6; IL-10, interleukin-10; L max , maximal length; LV, left ventricle; LVEDD, left vetricular end-diastolic diameter; LVEDP, left vetricular end-diastolic pressure; LVESD, left vetricular end-systolic diameter; LVPWd, diastolic left vetricular posterior wall thickness; LVPWs, systolic left vetricular posterior wall thickness; LVSP, left vetricular systolic pressure; MAP, mean arterial pressure; NF-κB, nuclear factor-κB; RT, resting tension; TGF-β 1 , transforming growth factor β 1 ; TNF-α, tumour necrosis factor α.
