Effects of calcium antagonists on high-energy phosphates in ischemic rat brain measured by31P NMR spectroscopy

Abstract

The effects of various calcium antagonists on the ATP, PCr, and P_i levels as well as intracellular pH in normal and ischemic rat brain were examined by 31P NMR spectroscopy using a surface coil. None of the calcium antagonists tested showed any effect in the nonischemic rat brain. However, when global ischemia was induced by cardiac arrest, the ensuring rapid decrease of ATP and PCr and concomitant increase of p_i were significantly retarded by dihydropyridine calcium antagonists, but not by verapamil. The fall in pH caused by ischemia was not affected by either drug. Barbiturates showed effects similar to calcium antagonists, whereas calcium agonists showed the opposite. These results suggest that dihydropyridine calcium antagonists, similar to barbiturates, decrease the high-energy phosphate consumption of the brain, which might be beneficial in instances where their production is severely hampered, e.g., during ischemia. © 1987 Academic Press, Inc.