Effects of Fasting, Hypoxia, Methylpalmoxirate and Oxfenicine on the Tissue-Levels of Long-Chain Acyl CoA and Acylcarnitine in the Rat Atria

Abstract

During hypoxia the atria from fasted rats exhibit a faster decline in the pacemaker and contractile activities than those from fed rats. Oxfenicine and methylpalmoxirate, inhibitors of carnitine palmitoyltransferase 1 (CPT 1), ameliorate these disturbances. Since the fasted rat atria have greater triacylglycerol stores and a faster lipolysis, and CPT 1 funnels fatty acid into ω-oxidation, the effects of fasting could be ascribed to the accumulation of amphipathic metabolites such as long-chain acyl CoA (LCCoA) and long-chain acylcarnitine (LCCa). Hence, this investigation aimed to assess whether the levels of these metabolites correlate with the effects of fasting and CPT 1 inhibitors. At the end of the prehypoxic equilibration period the fasted rat atria had a 6.5-fold greater content of LCCa than those of the fed rats and methylpalmoxirate impeded the increase. During hypoxia the LCCoA content increased 9-fold in the fasted rat atria, LCCa levels were 3.6-fold greater in the fasted than in the fed group, and free-CoA and free-carnitine showed a significant fall. The increases of LCCoA and LCCa as well as the fall in free-CoA were abolished by both inhibitors. The decrease of free-carnitine was impeded by methylpalmoxirate, but oxfenicine unexpectedly decreased its concentration in both nutritional groups. These data suggest that: (1) the atrial CPT 1 activity is enhanced during fasting, (2) in the hypoxic atria levels of LCCoA and LCCa were closely correlated with the noxious effects of fasting and the amelioration effected by CPT 1 inhibitors, and (3) the effects of amphipathic metabolites during oxygen deprivation can be attenuated by pharmacological interventions.