Dantrolene: effects on abnormal intracellular Ca(2+) handling and inotropy in postinfarcted rat myocardium.

ABSTRACT

The present study was designed to investigate the effects of dantrolene on intracellular Ca(2+) ([Ca(2+)](i)) handling and inotropy in rat infarcted myocardium. Dantrolene-treated rats with myocardial infarction were placed into two different dosage groups. The infarcted control group received placebo only. Isometric contractility and intracellular Ca(2+) transients were recorded simultaneously in isolated papillary muscles. Diastolic [Ca(2+)](i) was significantly lower in muscle preparations from infarcted rats receiving dantrolene compared to the placebo control group. Additionally, treatment with dantrolene in infarcted rats significantly improved the inotropic response to 10(-4) M isoproterenol. The protein levels of the sarcoplasmic reticulum Ca(2+) ATPase were increased in infarcted rat hearts with dantrolene treatment. We conclude that dantrolene improved the inotropic response to beta-adrenoceptor stimulation in rat postinfarcted myocardium, which is related to improved intracellular Ca(2+) handling, and lowered diastolic Ca(2+) concentration.