Nitric oxide and prostacyclin pathways: an integrated mechanism that limits myocardial infarction progression in anaesthetized rats.
Nitric oxide (NO) and cyclooxygenase-derived prostaglandins, such as prostacyclin (PGI2), are involved in vascular homeostasis. To better understand the reciprocal role of both NO and PGI2 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 PGI2-increased in the circulation associated to a reduction of thromboxane B2 (TXB2) in the blood. Defibrotide displays a cardioprotection by increasing PGI2 release and by reducing TXB2 in the blood. Naproxen was devoid a lower protecting activity on myocardial infarction, and PGI2 inhibition may have played a critical role in this context. The results suggested that the increase of both NO and PGI2 brings about a cascade of integrated cellular and molecular events which are of paramount importance in prevention of myocardial ischemic insult.
Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy. giuseppe.rossoni@unimi.it
Giuseppe
G
Rossoni
Barbara
B
Manfredi
Vito
V
De Gennaro Colonna
Anna Teresa
AT
Brini
Gianluca
G
Polvani
Maria Giovanna
MG
Clement
Ferruccio
F
Berti
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D011464:Epoprostenol / Q000097:blood*; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009288:Naproxen / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood*; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000097:blood
D002316:Cardiotonic Agents; D011089:Polydeoxyribonucleotides; D009569:Nitric Oxide; C036901:defibrotide; D013929:Thromboxane B2; D009288:Naproxen; D001120:Arginine; D011464:Epoprostenol; D009195:Peroxidase; D003402:Creatine Kinase; D007548:Isosorbide Dinitrate; C094069:nitronaproxen