title: Exercise training alters left ventricular geometry and attenuates heart failure in dahl salt-sensitive hypertensive rats.
abstract: The clinical efficacy of exercise training in individuals with heart failure is well established, but the mechanism underlying such efficacy has remained unclear. An imbalance between cardiac hypertrophy and angiogenesis is implicated in the transition to heart failure. We investigated the effects of exercise training on cardiac pathophysiology in hypertensive rats. Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age were assigned to sedentary or exercise (swimming)-trained groups at 9 weeks. Exercise training attenuated the development of heart failure and increased survival, without affecting blood pressure, at 18 weeks. It also attenuated left ventricular concentricity without a reduction in left ventricular mass or impairment of cardiac function. Interstitial fibrosis was increased and myocardial capillary density was decreased in the heart of sedentary rats, and these effects were attenuated by exercise. Exercise potentiated increases in the phosphorylation of Akt and mammalian target of rapamycin observed in the heart of sedentary rats, whereas it inhibited the downregulation of proangiogenic gene expression apparent in these animals. The abundance of the p110alpha isoform of phosphatidylinositol 3-kinase was decreased, whereas those of the p110gamma isoform of phosphatidylinositol 3-kinase and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase were increased, in the heart of sedentary rats, and all of these effects were prevented by exercise. Thus, exercise training had a beneficial effect on cardiac remodeling and attenuated heart failure in hypertensive rats, with these effects likely being attributable to the attenuation of left ventricular concentricity and restoration of coronary angiogenesis through activation of phosphatidylinositol 3-kinase(p110alpha)-Akt-mammalian target of rapamycin signaling.
authors.affiliation: Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya 461-8673, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyachi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yazawa
authors.forename: Mayuko
authors.initials: M
authors.lastname: Furukawa
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ohtake
authors.forename: Takao
authors.initials: T
authors.lastname: Nishizawa
authors.forename: Katsunori
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Toyoharu
authors.initials: T
authors.lastname: Yokoi
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Kojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Murate
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Koike
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004452:Echocardiography; D005355:Fibrosis; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D006973:Hypertension / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D053208:Kaplan-Meier Estimate; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt