Effects of methylpalmoxirate on isolated rat atria.
The aim of the investigation was to assess whether endogenous triacylglycerol contributes to the maintenance of the contractile and pacemaker activities of the isolated atria from fed and fasted rats. To attain this information, the atria were treated with methylpalmoxirate which is a potent inhibitor of carnitine palmitoyltransferase I. In the presence of glucose, methylpalmoxirate abolished the lipolysis without affecting peak developed tension or the atrial rate. When exposed to a substrate-free medium containing 2-deoxyglucose, the atria displayed a progressive fall of the pacemaker frequency, a pronounced decay of contractile strength and the appearance of contracture. These derangements appeared faster in the atria from fed rats coinciding with a smaller triacylglycerol mobilization. Methylpalmoxirate suppressed triacylglycerol breakdown, increased the contracture strength, accelerated the fall of the atrial rate and in a significant number of fasted atria it led to a complete cessation of the spontaneous contractions. The decline of the peak tension was not altered by the inhibitor, probably because the contractile strength was too weak in the glucose-free medium, so that additional negative inotropic effects were not detectable. These data suggest that exogenous glucose in addition to that derived from glycogen meet the atrial energy requirements when the fatty acid oxidation is hindered. The deleterious effects exerted by methylpalmoxirate after the glucose metabolism was eliminated indicate that endogenous triacylglycerol supports, at least partly, the atrial functions.
Varela
A
A
Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Carregal
M
M
Bruno-Magnasco
C
C
Espósito
S
S
Savino
E A
EA
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D004734:Energy Metabolism / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008066:Lipolysis / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D004852:Epoxy Compounds; D011422:Propionates; D014280:Triglycerides; D002334:Carnitine O-Palmitoyltransferase; C017522:methyl 2-tetradecylglycidate