A large body of evidence indicates that the inflammatory response plays an important role in the pathophysiology of myocardial ischemia injury. Melanocortin peptides have a protective effect in animals and humans in conditions of severe tissue hypoxia due to acute hemorrhage or prolonged respiratory arrest, and in a rat model of myocardial ischemia followed by reperfusion. This protective effect of melanocortins seems mainly due to a peculiar anti-inflammatory activity. Accumulating data, in fact, obtained in several models of experimental inflammation support this notion. So, we investigated in anesthetized rats the influence of the long-acting melanocortin [Nle4, D-Phe7] -melanocyte-stimulating hormone (NDP-MSH) on the damage induced by a permanent coronary artery occlusion. Ischemia was produced by occlusion of the left anterior descending coronary artery. The amount of healthy myocardial tissue was measured, 72 hours after occlusion, on immunohistologically stained serial sections. In saline-treated rats, the amount of healthy myocardial tissue (evaluated after anti-actin immunoreaction and calculated as a percentage of the myocardial volume of the lateral wall of the left ventricle) was much reduced (23.751.61%, n=12), while in rats treated i.p. with NDP-MSH (162 nmol/kg every 12 h) it was significantly higher (71.052.42%, n=11; P<0.001). In control rats, a marked inflammatory cell accumulation was found inside the ischemic tissue, and the expression of the cytoplasmic apoptotic bodies (evaluated after anti-bcl2 immunoreaction) was very high. In NDP-MSH-treated rats a weak inflammatory cell infiltration was detected, and no expression of cell apoptotic bodies was found. The present data show that, during myocardial ischemia, NDP-MSH is able to cause a significant reduction of both inflammatory cell infiltration and infarct size. The possible mechanisms of the protective effects of melanocortins in myocardial ischemia most likely involve the peculiar anti-inflammatory activity of these peptides. For such anti-inflammatory activity, a brain involvement could be postulated, on the basis of the recently recognized “cholinergic anti-inflammatory pathway” and of the well-known central effects of melanocortins.
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