title: Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained beta-adrenergic hyperactivity.
abstract: 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 beta-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 alpha, interleukin-6, interleukin-10 and transforming growth factor beta(1) (TGF-beta(1)) in the tissue. NF-B 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 alpha and interleukin-6, as well as TGF-beta(1) mRNA, were increased. In addition, the NF-B 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-beta(1) mRNA. Thus, exercise training in a model of beta-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.
authors.affiliation: Department of Medicine, Cardiology Division, Federal University of São Paulo, (UNIFESP), São Paulo, SP, Brazil. andreyserra@gmail.com
authors.forename: Andrey J
authors.initials: AJ
authors.lastname: Serra
authors.forename: Marília H H
authors.initials: MH
authors.lastname: Santos
authors.forename: Danilo S
authors.initials: DS
authors.lastname: Bocalini
authors.forename: Ednei L
authors.initials: EL
authors.lastname: Antônio
authors.forename: Rozeli F
authors.initials: RF
authors.lastname: Levy
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Santos
authors.forename: Maria L
authors.initials: ML
authors.lastname: Higuchi
authors.forename: José A
authors.initials: JA
authors.lastname: Silva
authors.forename: Flávio C
authors.initials: FC
authors.lastname: Magalhães
authors.forename: Valério G
authors.initials: VG
authors.lastname: Baraúna
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.forename: Paulo J F
authors.initials: PJ
authors.lastname: Tucci
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D004452:Echocardiography; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D016207:Cytokines; D016328:NF-kappa B; D011943:Receptors, Adrenergic, beta; D014409:Tumor Necrosis Factor-alpha; D007545:Isoproterenol