PP081 Nitic Oxide Mediated Effects of Nebivolol in Myocardial Infarction: The Source of Nitric Oxide

Abstract

Objective: After MI, LV remodelling is one of the major causes of death. We previously showed the NO mediated beneficial effects of nebivolol in rat MI model, in this study we aimed to determine the source of NO. Methods: Rats were divided into four groups: sham operated (sham-control), MI-induced (MI-control), immediate nebivolol loaded (MI-neb1), orally nebivolol treated (MI-neb2). MI was induced by the ligation of the LAD. NOS related mechanisms were assessed either in acute and sub-acute period of MI by histologic, hemodynamic and biologic studies. Results: Compared to MI-control rats, physiological functions of LV (LVEDP, D!dp/dt) were prevented in nebivolol treated groups. Improvements in anatomical parameters (LEV, HW, LVW/HW) were consistent with functional improvement. Oxidative (decreased MDA, increased SOD) and nitrosative (decreased ONOO-) damage were limited also. Most dramatic change was seen in the nNOS labelling.The decrease in iNOS labelling was also prominent too. Conclusions: NOS mediated mechanisms of nebivolol can be summarized as: 1) diminishing iNOS expression together with restoration of MI induced eNOS activation both in vascular bed and myocytes at the acute period of MI, and 2) prevention of deterioration in nNOS expression in myocardial cells at the sub-acute period of MI.