Reduced glycolysis by nisoldipine treatment of ischemic heart

Calcium entry blockers seem useful for energy conservation in the ischemic heart. Their exact mechanism of action, however, remains uncertain. In this study we investigated the effect of 30 nM nisoldipine on carbohydrate metabolism in isolated rat heart perfused with glucose-containing medium. Nisoldipine increased flow 1.5-fold and reduced apex displacement 60%. We induced ischemia by lowering the perfusion pressure from 72 to 14 mm Hg, which resulted in a flow reduction in untreated hearts by 80%. Lactate production rose 16-fold, glucose utilization increased fourfold, and the heart glycogen content decreased by 32%. Nisoldipine treatment diminished ischemic lactate release by 77%. It decreased glucose utilization to normoxic levels and reduced glycogen breakdown to a value intermediate to the ischemic and normoxic ones. We conclude that nisoldipine reduces glycolysis in the ischemic heart. Consequently, it appears that the ATP-saving effect of nisoldipine during ischemia, reported elsewhere, is due to a lower energy demand rather than increased ATP production.