DIHYDROPYRIDINE CALCIUM-ANTAGONISTS REDUCE THE CONSUMPTION OF HIGH-ENERGY PHOSPHATES IN THE RAT-BRAIN - A STUDY USING COMBINED P-31/H-1 MAGNETIC-RESONANCE SPECTROSCOPY AND P-31 SATURATION TRANSFER

  • 1 November 1989
    • journal article
    • research article
    • Vol. 251  (2) , 700-706
Abstract
The disappearance of high-energy phosphates (HEPs) in the rat brain during global ischemia induced by cardiac arrest is slowed down significantly by dihydropyridine Ca antagonists (DCAs) compared to controls. Two mechanisms might account for this effect: increased HEP production via anaerobic glycolysis or decreased HEP consumption. In order to obtain more insight into the underlying mechanisms of ATP preservation we have studied in the rat the effect of the DCAs isradipine, darodipine and nimodipine on the cerebral steady-state levels of HEPs and lactate as well as the intracellular pH value during global ischemia using combined 31P/1H magnetic resonance spectroscopy. We have found that ATP preservation in DCA-treated animals is not associated with significantly higher postischemic lactate levels (lactate/N-acetylaspartate 0.97 .+-. 0.08 for isradipine at a dose of 2.5 mg/kg i.p.) or lower pH values (6.40 .+-. 0.03) as compared to control rats (lactate/N-acetylaspartate = 0.94 .+-. 0.13, pH = 6.49 .+-. 0.03). This is in contrast to hyperglycemic rats, in which similar preservation of ATP levels during ischemia was observed; however, at the expense of a larger drop in brain pH (6.22 .+-. 0.09) and a concomitant increase in cerebral lactate (lactate/N-acetylaspartate = 1.40 .+-. 0.09). These results strongly favor reduced ATP consumption to be the cause for the protective effect of DCAs. In order to further support this interpretation we have measured, using the 31P saturation transfer method, the effect of DCAs on the flux through the creatine kinase forward reaction (phosphocreatine + ADP + H+ .fwdarw. creatine + ATP) in intact rats assuming that like in the heart this reaction is coupled to the cerebral ATP turn over. The data show that isradipine significantly reduces the flux through the creatine kinase reaction (-23 .+-. 6%) as compared to controls. Thus, both global ischemia and saturation transfer experiments support the interpretation that DCAs reduce the HEP consumption in the rat brain.