Dantrolene: effects on abnormal intracellular Ca(2+) handling and inotropy in postinfarcted rat myocardium.
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.
Min
Jiang-Yong
JY
Cardiovascular Division, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215, USA.
Meissner
Achim
A
Feng
Xin
X
Wang
Jianan
J
Malek
Sohail
S
Wang
Ju-Feng
JF
Simon
Rudiger
R
Morgan
James P
JP
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism; D021983:Cyclophilins / Q000737:chemistry / Q000378:metabolism; D003620:Dantrolene / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013997:Time Factors; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D021983:Cyclophilins; D003620:Dantrolene; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban