Force-frequency response in isoproterenol-induced hypertrophied rat heart

Rate-dependent force production was investigated using small trabecular muscle from control and hypertrophied rat cardiac muscle. Cardiac hypertrophy was induced by daily subcutaneous injection of isoproterenol (0.3 mg/kg body weight) for 12 days. The force-frequency relationship, for the control rat myocardium, is clearly biphasic. A stepped increase in stimulation frequency from 0.1 to 0.5 Hz results in a decrease in contractile force (negative phase). However, at higher stimulation frequency above 0.5 Hz, an increased contractile force is revealed (positive phase). Membrane action potential duration (APD50) was used to reflect sarcolemmal Ca2+ influx. The frequency-dependent increase in APD50 and the ability of nifedipine, a sarcolemmal L-type Ca2+ channel blocker, to eliminate the positive-force frequency response, indicate that sarcolemmal Ca2+ influx is important for force development at high stimulation frequency. Relative Ca2+ content of sarcoplasmic reticulum is estimated from rapid cooling contractures. The parallel change of rapid cooling contractures and twitch force suggests that the sarcoplasmic reticulum Ca2+ content alters with varying frequencies of stimulation. Isoproterenol-induced hypertrophied muscle shows a greater contractile force, increased nifedipine-sensitive force development and prolonged APD50 compared to controls. These data suggest a greater availability of intracellular Ca2+ to activate contraction in hypertrophied muscle, possibly by amplified Ca2+ influx via L-type channel.