Anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts

Background: activated cardiac apoptosis was found in hearts from hypertensive animals, but little information regarding the effects of exercise training on cardiac apoptosis in hypertension is available. The purpose of this study was to evaluate the anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts. Methods: 28 spontaneously hypertensive rats were divided into sedentary group (SHR) or underwent running exercise on treadmill for 1 h/day, 5 sessions/wk, for 12 wk (SHR-EX). Fourteen age-matched Wistar Kyoto rats served as a sedentary normotensive group (WKY). After exercise training or sedentary status, the excised hearts were measured by hemotoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) assay, and Western blotting. Results: fewer TUNEL-positive apoptotic cells were in SHR-EX groups than those in SHR. Protein levels of Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fasdependent apoptotic pathways), as well as Bid, t-Bid, Bad, p-Bad, Bak, cytochrome c, activated caspase 9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the SHR-EX group compared with the SHR group. Protein levels of IGF-1, IGF-1R, p-PI3K, p-Akt, p-Bad, and Bcl2 (cardiac pro-survival pathway) become more activated in SHR-EX groups than SHR and WKY. Conclusions: exercise training prevented hypertension-enhanced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced cardiac pro-survival pathway in rat models. Our findings demonstrate new therapeutic effects of exercise training on hypertensive hearts for preventing apoptosis and enhancing survival.