Jpn. J. Pharmacol. 74 (2), 147-153 (1997)

Beneficial Effects of Dilazep on the Palmitoyl-L-carnitine-Induced Derangements in Isolated, Perfused Rat Heart: Comparison with Tetrodotoxin

Akiyoshi Hara, Johji Arakawa, Hiroko Hashizume and Yasushi Abiko

Department of Pharmacology, Asahikawa Medical College, Asahikawa 078, Japan

Abstract: The present study was carried out to determine the effect of dilazep, having an inhibitory effect on the Na+ channel, on the mechanical dysfunction and metabolic derangements induced by palmitoyl-L-carnitine in isolated rat heart and to compare the effect of dilazep with that of tetrodotoxin, a specific inhibitor of the Na+ channel. Rat hearts were perfused aerobically at a constant flow according to Langendorff's technique and paced electrically. Palmitoyl-L-carnitine (5 microM) decreased the left ventricular developed pressure and increased the left ventricular end diastolic pressure (i.e., it produced mechanical dysfunction), decreased the tissue level of adenosine triphosphate and increased the tissue level of adenosine monophosphate (i.e., it produced metabolic derangements). These mechanical and metabolic alterations induced by palmitoyl-L-carnitine were attenuated by either dilazep (1 microM) or tetrodotoxin (3 microM). On the other hand, neither dilazep nor tetrodotoxin modified the mechanical function and energy metabolism of the normal (palmitoyl-L-carnitine-untreated) heart. These results suggest that inhibition of the Na+ channel with dilazep or tetrodotoxin is responsible, at least in part, for attenuating the palmitoyl-L-carnitine-induced mechanical dysfunction and metabolic derangements in the heart.

Keywords: Dilazep, Tetrodotoxin, Long-chain acylcarnitine, Na+ channel, Heart (rat)