Energy conservation by nisoldipine in ischaemic heart

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Abstract
1 We studied the effect of the calcium entry blocker nisoldipine on ATP catabolism in the rat heart, perfused according to Langendorff. Even 1 nM nisoldipine induced vasodilatation; concentrations of 30 nM and higher caused significant negative inotropy. 2 The drug had a very strong affinity for silicon rubber tubing. 3 Myocardial ischaemia was induced by lowering the perfusion pressure, which reduced flow without nisoldipine by 85%. The efflux of purine nucleosides and oxypurines rose 14 fold. Nisoldipine reduced this efflux of ATP catabolites dose-dependently. The highest concentration, 300 nM, suppressed ischaemic purine production completely. 4 The action of the drug was antagonized by an increase in Ca2+-concentration in the perfusion fluid. 5 We also showed the protective effect of nisoldipine on adenine nucleotides in freeze-clamped hearts. A concentration of 20 nM partially prevented the reduction of ATP and adenylate energy charge due to ischaemia. 6 We conclude that relatively low doses of nisoldipine effectively prevent ATP breakdown in ischaemic rat heart.