Spermine-induced negative inotropic effect in isolated rat heart, is mediated through the release of ATP

Gustavo Guevara-Balcázar, Enrique Querejeta-Villagómez, Oskar Nuevo-Adalla, Alejandra Orozco-Guillen, Ivan Rubio-Gayosso, Jose R. Hernández-Castillo, Miguel Zamora-Garza, Guillermo Ceballos-Reyes

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Putrescine, spermidine and spermine are natural compounds found in up to millimolar concentrations in eukaryotic and prokaryotic cells. At physiologic pH, the polyamines are protonated (+2, +3 and +4 charges), their polycationic properties lead to the assumption that they could affect physiological systems by binding to anionic sites of the cellular membrane and/or by modulating ion channels. At the cardiovascular level, their effects are not completely understood. However, these compounds may be able to exert the induction of synthesis and release of cellular mediators. In an attempt to explore this possibility, we used the isolated and perfused rat heart, Langendorff, model in order to evaluate the inotropic effects of these polyamines, putrescine, spermidine and spermine. Dose-response curves (0.1-0.6mM) for putrescine, spermidine and spermine were constructed; with the finding that spermine had the largest negative effect. The obtained effects were not blocked by nitric oxide synthesis inhibitors (L-NAME), H1 and H2 receptor antagonists (Brompheniramine and Cimetidine) or by Glibenclamide, an antagonist of ATP-sensitive K+ channels. We found that spermine-induced and increased ATP concentration in cardiac effluents. Reactive Blue, a P2y purinoreceptor antagonist and Aminophylline, an unspecific adenosine receptor antagonist, blocked the spermine-induced effects. These results showed that ATP, at least in part, is responsible of the spermine cardiovascular effects. Adenosine was shown to also play an important role on those effects.

Original languageEnglish
Pages (from-to)157-161
Number of pages5
JournalBiochemical Pharmacology
Volume66
Issue number1
DOIs
StatePublished - 1 Jul 2003

Keywords

  • Heart
  • Inotropism
  • Polyamines
  • Pressure
  • Spermine
  • Ventricular contraction force

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