EFFECTS OF FASTING, HYPOXIA, METHYLPALMOXIRATE AND OXFENICINE ON THE TISSUE-LEVELS OF LONG-CHAIN ACYL COA AND ACYLCARNITINE IN THE RAT ATRIA

During hypoxia the atria from fasted rats exhibit a faster decline in the pacemaker and contractile activities than those from fed rats. Oxf enicine and methylpalmoxirate, inhibitors of carnitine palmitoyltransf erase 1 (CPT 1), ameliorate these disturbances. Since the fasted rat a tria have greater triacylglycerol stores and a faster lipolysis, and C PT 1 funnels fatty acid into beta-oxidation, the effects of fasting co uld be ascribed to the accumulation of amphipathic metabolites such as long-chain acyl CoA (LCCoA) and long-chain acylcarnitine (LCCa). Henc e, this investigation aimed to assess whether the levels of these meta bolites correlate with the effects of fasting and CPT 1 inhibitors. At the end of the prehypoxic equilibration period the fasted rat atria h ad a 6.5-fold greater content of LCCa than those of the fed rats and m ethylpalmoxirate impeded the increase. During hypoxia the LCCoA conten t 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-car nitine showed a significant fall. The increases of LCCoA and LCCa as w ell as the fall in free-CoA were abolished by both inhibitors. The dec rease of free-carnitine was impeded by methylpalmoxirate, but oxfenici ne unexpectedly decreased its concentration in both nutritional groups . These data suggest that: (1) the atrial CPT 1 activity is enhanced d uring fasting, (2) in the hypoxic atria levels of LCCoA and LCCa were closely correlated with the noxious effects of fasting and the amelior ation effected by CPT 1 inhibitors, and (3) the effects of amphipathic metabolites during oxygen deprivation can be attenuated by pharmacolo gical interventions.