1. Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart.
- Author
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Leosco D, Rengo G, Iaccarino G, Golino L, Marchese M, Fortunato F, Zincarelli C, Sanzari E, Ciccarelli M, Galasso G, Altobelli GG, Conti V, Matrone G, Cimini V, Ferrara N, Filippelli A, Koch WJ, and Rengo F
- Subjects
- Adrenergic beta-Agonists pharmacology, Animals, Coronary Circulation, Coronary Vessels drug effects, Coronary Vessels metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Heart Failure diagnostic imaging, Heart Failure etiology, Heart Failure metabolism, Isoproterenol pharmacology, Male, Myocardial Contraction, Myocardial Infarction diagnostic imaging, Myocardial Infarction metabolism, Myocardial Infarction physiopathology, Myocardium enzymology, Myocardium pathology, Nitric Oxide Synthase Type II metabolism, Nitric Oxide Synthase Type III, Proto-Oncogene Proteins c-akt metabolism, Rats, Rats, Wistar, Receptors, Adrenergic, beta drug effects, Time Factors, Ultrasonography, Vascular Endothelial Growth Factor A metabolism, Ventricular Function, Left, Ventricular Remodeling, Coronary Vessels physiopathology, Heart Failure physiopathology, Myocardial Infarction complications, Myocardium metabolism, Neovascularization, Physiologic drug effects, Physical Exertion, Receptors, Adrenergic, beta metabolism, Signal Transduction drug effects
- Abstract
Aims: We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated beta-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise., Methods and Results: Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 +/- 5%), increased LV end diastolic pressure (20.9 +/- 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac beta-adrenergic receptor downregulation and desensitization., Conclusions: Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.
- Published
- 2008
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