PHYSICAL-TRAINING ALTERS THE PATHOGENESIS OF PACING-INDUCED HEART-FAILURE THROUGH ENDOTHELIUM-MEDIATED MECHANISMS IN AWAKE DOGS

Background Beneficial effects of exercise training on cardiovascular f unction in chronic heart failure (CHF) have been suggested previously, but the underlying mechanisms are unknown. We tested whether daily ex ercise training improves systemic hemodynamics and preserves endo thel ium-mediated vasodilator function during development of heart failure. Methods and Results Fifteen dogs were surgically instrumented for hem odynamic measurements. One group of dogs underwent 4 weeks of cardiac pacing (210 bpm for 3 weeks and 240 bpm during week 4), and another gr oup underwent pacing plus daily exercise training (4.4+/-0.3 km/h, 2 h /d). Pacing-alone dogs developed CHF characterized by typical hemodyna mic abnormalities, blunted endothelium-mediated vasodilator function i n coronary and femoral circulations, and decreased gene expression of endothelial constitutive nitric oxide synthase (ECNOS, normalized to G APDH expression; normal, 1.15+/-0.31 versus CHF, 0.29+/-0.08, P<.05). Exercise training preserved normal hemodynamics at rest, endothelium-m ediated vasodilator function, and gene expression of ECNOS (0.72+/-0.1 6 versus normal, P=NS). Inhibition of NO synthesis (nitro-L-arginine) in exercise-trained dogs abolished the preserved endothelium-mediated vasodilation of epicardial coronary arteries and elevated left ventric ular end-diastolic pressure (7.7+/-0.3 to 19+/-3.4 mm Hg, P<.05), sugg esting that the preservation of resting hemodynamics was in large part due to preserved endothelial function concealing the underlying CHF s tate. Conclusions Long-term exercise training altered the natural hist ory of heart failure due to rapid cardiac pacing. One of the underlyin g mechanisms is through the preservation of endothelial vasodilator fu nction.