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pubmed:abstractText |
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. The drug had a very strong affinity for silicon rubber tubing. 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. The action of the drug was antagonized by an increase in Ca2+-concentration in the perfusion fluid. 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. We conclude that relatively low doses of nisoldipine effectively prevent ATP breakdown in ischaemic rat heart.
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