title: Exercise training can prevent cardiac hypertrophy induced by sympathetic hyperactivity with modulation of kallikrein-kinin pathway and angiogenesis.
abstract: Sympathetic hyperactivity induces adverse effects in myocardial. Recent studies have shown that exercise training induces cardioprotection against sympathetic overload; however, relevant mechanisms of this issue remain unclear. We analyzed whether exercise can prevent pathological hypertrophy induced by sympathetic hyperactivity with modulation of the kallikrein-kinin and angiogenesis pathways. Male Wistar rats were assigned to non-trained group that received vehicle; non-trained isoproterenol treated group (Iso, 0.3 mg kg(-1) day-(1)); and trained group (Iso+Exe) which was subjected to sympathetic hyperactivity with isoproterenol. The Iso rats showed hypertrophy and myocardial dysfunction with reduced force development and relaxation of muscle. The isoproterenol induced severe fibrosis, apoptosis and reduced myocardial capillary. Interestingly, exercise blunted hypertrophy, myocardial dysfunction, fibrosis, apoptosis and capillary decreases. The sympathetic hyperactivity was associated with high abundance of ANF mRNA and β-MHC mRNA, which was significantly attenuated by exercise. The tissue kallikrein was augmented in the Iso+Exe group, and kinin B1 receptor mRNA was increased in the Iso group. Moreover, exercise induced an increase of kinin B2 receptor mRNA in myocardial. The myocardial content of eNOS, VEGF, VEGF receptor 2, pAkt and Bcl-2 were increased in the Iso+Exe group. Likewise, increased expression of pro-apoptotic Bad in the Iso rats was prevented by prior exercise. Our results represent the first demonstration that exercise can modulate kallikrein-kinin and angiogenesis pathways in the myocardial on sympathetic hyperactivity. These findings suggest that kallikrein-kinin and angiogenesis may have a key role in protecting the heart.
authors.affiliation: Universidade Nove de Julho (Uninove), Programa de Pós-graduação em Ciências da Reabilitação, Rua Vergueiro, São Paulo, SP, Brazil; Universidade Nove de Julho (Uninove), Programa de Pós-graduação em Medicina, Rua Vergueiro, São Paulo, SP, Brazil.
authors.forename: José Antônio
authors.initials: JA
authors.lastname: Silva
authors.affiliation: Universidade Nove de Julho (Uninove), Programa de Pós-graduação em Ciências da Reabilitação, Rua Vergueiro, São Paulo, SP, Brazil.
authors.forename: Eduardo Tadeu
authors.initials: ET
authors.lastname: Santana
authors.affiliation: Universidade Nove de Julho (Uninove), Programa de Pós-graduação em Ciências da Reabilitação, Rua Vergueiro, São Paulo, SP, Brazil.
authors.forename: Martha Trindade
authors.initials: MT
authors.lastname: Manchini
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Rua Napoleão de Barros, São Paulo, SP, Brazil.
authors.forename: Ednei Luis
authors.initials: EL
authors.lastname: Antônio
authors.affiliation: Universidade Nove de Julho (Uninove), Programa de Pós-graduação em Ciências da Reabilitação, Rua Vergueiro, São Paulo, SP, Brazil.
authors.forename: Danilo Sales
authors.initials: DS
authors.lastname: Bocalini
authors.affiliation: Universidade de São Paulo, Incor. Av. Dr. Enéas de Carvalho Aguiar, São Paulo, SP, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Rua Napoleão de Barros, São Paulo, SP, Brazil.
authors.forename: Paulo José Ferreira
authors.initials: PJ
authors.lastname: Tucci
authors.affiliation: Universidade Nove de Julho (Uninove), Programa de Pós-graduação em Ciências da Reabilitação, Rua Vergueiro, São Paulo, SP, Brazil; Universidade Nove de Julho (Uninove), Programa de Pós-graduação em Medicina, Rua Vergueiro, São Paulo, SP, Brazil.
authors.forename: Andrey Jorge
authors.initials: AJ
authors.lastname: Serra
mesh_terms: D000818:Animals; D017209:Apoptosis; D002196:Capillaries / Q000473:pathology; D006332:Cardiomegaly / Q000503:physiopathology* / Q000517:prevention & control*; D024022:Fibrillar Collagens / Q000378:metabolism; D007545:Isoproterenol; D007610:Kallikreins / Q000378:metabolism*; D007705:Kinins / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D010805:Physical Conditioning, Animal; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D024022:Fibrillar Collagens; D007705:Kinins; D007610:Kallikreins; D007545:Isoproterenol