Improvement of cardiac function and beta-adrenergic signal transduction by propionyl L-carnitine in congestive heart failure due to myocardial infarction.
OBJECTIVE
Earlier studies have revealed beneficial effects of metabolic therapy in animals with congestive heart failure (CHF) due to myocardial infarction. Because heart failure is also associated with attenuated response to catecholamines, we examined the effects of propionyl L-carnitine (PLC) (a carnitine derivative) therapy on the beta-adrenoceptor (beta-AR) signal transduction in the failing heart.


METHODS
Heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated with or without 100 mg/kg (intraperitoneally, daily) PLC for 5 weeks. The animals were assessed for their left ventricular function and inotropic responses to isoproterenol. Crude membranes were isolated from the remote, nonischemic (viable) left ventricle and examined for changes in beta-AR and adenylyl cyclase (AC) activity.


RESULTS
Animals with heart failure exhibited depressions in ventricular function, positive inotropic response to isoproterenol, beta-AR receptor density and basal AC activity; these changes were also attenuated by PLC treatment. The stimulation of AC activities with isoproterenol, 5'-guanyl imidodiphosphate, forskolin and sodium fluoride was decreased in the failing hearts and these changes were also prevented by PLC treatment.


CONCLUSIONS
The results indicate that metabolic therapy with PLC not only attenuates the defects in heart function but also prevents changes in the beta-AR signal transduction in CHF due to myocardial infarction.
Sethi
Rajat
R
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Canada.
Wang
Xi
X
Ferrari
Roberto
R
Dhalla
Naranjan S
NS
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D011943:Receptors, Adrenergic, beta; C003223:propionylcarnitine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002331:Carnitine