Palmitoyl-L-carnitine modifies the myocardial levels of high-energy phosphates and free fatty acids.
Long-chain acylcarnitines, such as palmitoyl-L-carnitine (PALCAR), are known to accumulate in the myocardium during ischemia. We examined whether exogenous PALCAR modifies the myocardial levels of high-energy phosphates (HEP) and free fatty acids (FFA) in the heart, and whether d-cis-diltiazem and l-cis-diltiazem, an optical isomer having less potent Ca2+ channel blocking action than d-cis-diltiazem, attenuate the PALCAR-induced myocardial changes. Rat hearts were perfused aerobically at a constant flow according to the Langendorff's technique, while being paced electrically. PALCAR (5 microM) decreased the tissue levels of adenosine triphosphate and creatine phosphate and increased the tissue level of adenosine monophosphate, and produced mechanical dysfunction. In addition, PALCAR (5 microM) increased markedly the tissue levels of FFA, especially those of arachidonic and palmitoleic acids, and the release of creatine kinase (CK) from the myocardium. These alterations in the myocardial levels of HEP and FFA induced by PALCAR were significantly attenuated by d-cis-diltiazem (15 microM) or l-cis-diltiazem (15 microM). Both drugs also attenuated the PALCAR-induced CK release. The present study demonstrates that PALCAR modifies the tissue levels of HEP and FFA in the heart and that both d-cis- and l-cis-diltiazem protect the myocardium against the PALCAR-induced changes through mechanisms other than Ca2+ channel blocking action.
Xiao
C Y
CY
Department of Pharmacology, Asahikawa Medical College, Japan.
Chen
M
M
Hara
A
A
Hashizume
H
H
Abiko
Y
Y
D000227:Adenine Nucleotides / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003402:Creatine Kinase / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D013053:Spectrophotometry
D000227:Adenine Nucleotides; D002121:Calcium Channel Blockers; D005230:Fatty Acids, Nonesterified; D010725:Phosphocreatine; D010172:Palmitoylcarnitine; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D004110:Diltiazem