Moderate vs. high exercise intensity: differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function.

OBJECTIVE Current guidelines are controversial regarding exercise intensity in cardiovascular prevention and rehabilitation. Although high-intensity training induces larger increases in fitness and maximal oxygen uptake (VO(2max)), moderate intensity is often recommended as equally effective. Controlled preclinical studies and randomized clinical trials are required to determine whether regular exercise at moderate versus high intensity is more beneficial. We therefore assessed relative effectiveness of 10-week HIGH versus moderate (MOD) exercise intensity on integrative and cellular functions. METHODS Sprague-Dawley rats performed treadmill running intervals at either 85%-90% (HIGH) or 65%-70% (MOD) of VO2max 1 h per day, 5 days per week. Weekly VO2max-testing adjusted exercise intensity. RESULTS HIGH and MOD increased VO2max by 71% and 28%, respectively. This was paralleled by intensity-dependent cardiomyocyte hypertrophy, 14% and 5% in HIGH and MOD, respectively. Cardiomyocyte function (fractional shortening) increased by 45% and 23%, contraction rate decreased by 43% and 39%, and relaxation rate decreased by 20% and 10%, in HIGH and MOD, respectively. Ca2+ transient time-courses paralleled contraction/relaxation, whereas Ca2+ sensitivity increased 40% and 30% in HIGH and MOD, respectively. Carotid artery endothelial function improved similarly with both intensities. EC50 for acetylcholine-induced relaxation decreased 4.3-fold in HIGH (p < 0.05) and 2.8-fold in MOD (p < 0.20) as compared to sedentary; difference HIGH versus MOD 1.5-fold (p = 0.72). Multiple regression identified rate of systolic Ca2+ increase and diastolic myocyte relengthening as main variables associated with VO2max. Cell hypertrophy, contractility and vasorelaxation also correlated significantly with VO2max. CONCLUSIONS The present study demonstrates that cardiovascular adaptations to training are intensity-dependent. A close correlation between VO2max, cardiomyocyte dimensions and contractile capacity suggests significantly higher benefit with high intensity, whereas endothelial function appears equivalent at moderate levels. Thus, exercise intensity emerges as an important variable in future preclinical and clinical investigations.