Nitric oxide and prostacyclin pathways: An integrated mechanism that limits myocardial infarction progression in anaesthetized rats

Giuseppe Rossoni, Barbara Manfredi, Vito De Gennaro Colonna, Anna Teresa Brini, Gianluca Polvani, Maria Giovanna Clement, Ferruccio Berti

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Nitric oxide (NO) and cyclooxygenase-derived prostaglandins, such as prostacyclin (PGI 2), are involved in vascular homeostasis. To better understand the reciprocal role of both NO and PGI 2 on myocardial infarction in the rat, we have investigated the cardioprotective effect of nitro-naproxen, isosorbide dinitrate (ISDN), l-arginine, defibrotide and naproxen. In this study, male Wistar rats were treated orally once a day for 5 consecutive days with the compounds under investigation and then, under anesthesia, the animals were subjected to acute myocardial ischemia (30 min) and reperfusion (120 min). Systemic blood pressure, left ventricular pressure and related parameters of cardiac mechanics were recorded. Ventricular arrhythmias and infarct size of the left ventricular wall were also evaluated. Furthermore, cardiac myeloperoxidase (MPO) and plasma creatine phosphokinase (CPK) activities were determined. Defibrotide, nitro-naproxen, ISDN and l-arginine all provided a cardioprotection characterized by significant prevention of arrhythmias with high survival rate of the rats. Infarct size restriction was paralleled by reduction of both cardiac MPO and plasma CK. Cardioprotection of nitro-naproxen, ISDN and l-arginine involve nitrites/nitrates and PGI 2-increased in the circulation associated to a reduction of thromboxane B 2 (TXB 2) in the blood. Defibrotide displays a cardioprotection by increasing PGI 2 release and by reducing TXB 2 in the blood. Naproxen was devoid a lower protecting activity on myocardial infarction, and PGI 2 inhibition may have played a critical role in this context. The results suggested that the increase of both NO and PGI 2 brings about a cascade of integrated cellular and molecular events which are of paramount importance in prevention of myocardial ischemic insult.

Original languageEnglish
Pages (from-to)359-366
Number of pages8
JournalPharmacological Research
Issue number4
Publication statusPublished - Apr 2006


  • Cardioprotection
  • Ischemia-reperfusion
  • Myocardial infarction
  • Nitric oxide
  • Prostacyclin

ASJC Scopus subject areas

  • Pharmacology


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