Cardioprotection with sildenafil, a selective inhibitor of cyclic 3′,5′-monophosphate-specific phosphodiesterase 5

S. Das, N. Maulik, D. K. Das, P. J. Kadowitz, T. J. Bivalacqua

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of sildenafil (Viagra®), a specific inhibitor of phosphodiesterase 5, on ischemic myocardium was examined using an isolated rat heart model. Rats were pretreated with sildenafil at doses ranging from 0.001 mg to 0.5 mg/kg body weight. After 60 min, isolated hearts were subjected to ischemia for 30 min followed by 2 h of reperfusion. The results demonstrated that at 0.05 mg/kg (and to some extent at 0.01 mg/kg), sildenafil provided significant cardioprotection as evidenced by improved ventricular recovery, a reduced incidence of ventricular fibrillation and decreased myocardial infarction. At higher doses, it caused a significant increase in the incidence of ventricular fibrillation while at very low doses it had no effect on cardiac function. As expected, sildenafil increased cyclic 3′,5′-monophosphate (cGMP) content in the heart. The results demonstrate for the first time that within a narrow dose range, sildenafil can protect the heart from ischemia/reperfusion injury, probably through a cGMP-signaling pathway.

Original languageEnglish (US)
Pages (from-to)213-219
Number of pages7
JournalDrugs under Experimental and Clinical Research
Volume28
Issue number6
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)

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