Pentoxifylline improves reoxygenation-induced contractile recovery through a nitric oxide-dependent mechanism in rat papillary muscles

Farzad Ebrahimi, Amir Reza Hajrasouliha, Sina Tavakoli, Hamed Sadeghipour, Mehdi Ghasemi, Bahareh Rahimzadeh Rofoui, Seyed Hossein Ahmadi, Ahmad Reza Dehpour

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In this study, the protective effect of pentoxifylline against hypoxia-reoxygenation injury and the possible involvement of nitric oxide (NO)-mediated pathways in this protection were investigated in isolated rat papillary muscles. Papillary muscles were excised and isolated in Krebs-Henseleit solution aerated with 95% O2 and 5% CO2. Hypoxia was simulated by substituting O2 with argon. Three sets of experiments, testing 30, 60, and 90 min of hypoxia, were performed. The effects of different pentoxifylline concentrations on papillary muscle contractile parameters and responsiveness to isoproterenol were assessed. To investigate the role of NO, N(ω)-nitro-L- arginine methyl ester was added before pentoxifylline treatment. Pentoxifylline did not show any inotropic effect on papillary muscles. Hypoxia caused a profound depression of contractile parameters, which was not affected by pentoxifylline treatment. Reoxygenation resulted in significant partial recovery of contractile parameters after 30 and 60 but not 90 min of hypoxia. In experiments with 30 and 60 min of hypoxia, reoxygenation-induced contractile recovery and responsiveness to isoproterenol were improved by pentoxifylline in a concentration-dependent fashion. These functional improvements were completely blocked by N(ω)-nitro-L-arginine methyl ester pretreatment. No improvement was observed in 90-min hypoxia experiment. In conclusion, pentoxifylline improved contractile recovery during reoxygenation and postreoxygenation responsiveness to β-adrenergic stimulation through the NO-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)571-577
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume47
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

Keywords

  • Contractility
  • Hypoxia/reoxygenation
  • Nitric oxide
  • Pentoxifylline

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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