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.