The influence of triamterene on isoproterenol-induced and spontaneous myocardial calcium uptake in cardiomyopathic hamsters.

In this study the influence of 2,4,7-triamino-6-phenylpteridine (triamterene) on isoproterenol-induced myocardial accumulation of calcium in cardiomyopathic hamsters in the prenecrotic phase of their disease was investigated (acute experiments). When triamterene is administered in increasing doses simultaneously with the standard dose of 1 mg/kg isoproterenol, a dose-dependent decrease in the isoproterenol-induced calcium accumulation can be observed. A dose of 60 mg/kg triamterene is fully effective in preventing the isoproterenol-provoked myocardial calcium accumulation. In addition under the influence of isoproterenol the myocardial magnesium and potassium contents drop. This decrease can be also avoided when triamterene is administered simultaneously. The action of triamterene on spontaneous myocardial calcium accumulation was also studied in the cardiomyopathic hamsters, which beginning on their 30th day of life chronically received triamterene over a period of 27 days (twice daily 60 mg/kg p.o.). Usually the spontaneous calcium accumulation runs in parallel with progressive myocardial necrotization starting about the 40th day of life. The chronic experiment was unsuccessful; the myocardial calcium content was even higher in the triamterene-treated animals than in the controls. The failure of the long-term experiment seems to result from uremia due to high doses of triamterene with metabolic alterations that have not yet been clarified. Neverthless, triamterene seems to possess a cardioprotective effect against myocardial calcium overload. As the substance could also maintain normal intracellular potassium and magnesium contents in the acute isoproterenol experiments a combined application of triamterene and calcium antagonistic drugs is suggested. By this combination not only transmembrane calcium conductivity is reduced but also intracellular calcium binding sites might be blocked by normalized intracellular magnesium and potassium contents.