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The purpose of this study was to investigate the acute effects of constant and variable resistance exercise on neuromuscular and endocrine responses during maximal strength and hypertrophic loadings.Thirteen young men (age = 28.4 ± 3.7 yr) took part in four loadings (maximal strength and hypertrophic loadings using both constant and variable resistance) in a counterbalanced order. Maximal strength loadings consisted of 15 sets of one repetition at 100% one-repetition maximum, and hypertrophic loadings consisted of five sets of 10 repetitions (initial load of 80% one-repetition maximum). Preloading, immediately postloading, 15 min postloading, and 30 min postloading tests consisted of maximal bilateral isometric leg press, venous blood samples (analyzed for total testosterone, growth hormone, and cortisol), and fingertip blood lactate samples. Concentric force and vastus lateralis, vastus medialis, rectus femoris, and biceps femoris EMG was recorded throughout each loading protocol and analyzed over 20° segments.Force and quadriceps EMG was greater from 120° to 180° knee angle (P < 0.05) during variable resistance hypertrophic loadings. Larger increases in concentric quadriceps muscle activation and slower recovery in isometric force and muscle activation were observed during variable resistance hypertrophic loadings. Preloading to postloading serum total testosterone, growth hormone, and cortisol concentration increased during variable resistance hypertrophic loading, whereas during constant resistance loadings, only growth hormone increased (P = 0.051). During 30 min postloading, growth hormone and cortisol concentrations remained elevated after both hypertrophic loadings.A greater level of neuromuscular fatigue and larger responses in serum hormone concentrations occurred after hypertrophic variable resistance loading. These findings indicate greater fatigability during variable resistance loading and that this fatigability influences acute hormonal responses.