Exercise training alters left ventricular geometry and attenuates heart failure in dahl salt-sensitive hypertensive rats.
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.
Miyachi
Masaaki
M
Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya 461-8673, Japan.
Yazawa
Hiroki
H
Furukawa
Mayuko
M
Tsuboi
Koji
K
Ohtake
Masafumi
M
Nishizawa
Takao
T
Hashimoto
Katsunori
K
Yokoi
Toyoharu
T
Kojima
Tetsuhito
T
Murate
Takashi
T
Yokota
Mitsuhiro
M
Murohara
Toyoaki
T
Koike
Yasuo
Y
Nagata
Kohzo
K
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
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt