ENDOTHELIAL DYSFUNCTION IN SYSTEMIC INFLAMMATORY RESPONSE SYNDROME: EFFICACY OF COMBINED THERAPY OF <i>β</i>-HYDROXY-<i>β</i>-METHYLGLUTARIL-COA-REDUCTASE INHIBITORS
One of the serious complications of systemic inflammation requiring pharmacological correction is endothelial dysfunction. Objective: to study the endothelial protective effects of statins (atorvastatin, rosuvastatin, nanorosuvastatin) and the combination of statins with L - arginine and darbepoetin in an experimental model of endotoxin - induced and L - NAME - induced endothelial dysfunction. Materials and methods. On the model of nitro - L - arginine methyl ester (L - NAME) and endotoxin - induced endothelial dysfunction, the endothelioprotective effect of β - hydroxy - β - methylglutaryl - CoA (HMG - CoA) reductase inhibitors (atorvastatin, rosuvastatin, nanorosuvastatin) in combination was studied with L - arginine and darbepoetin. In addition, the activity of these drugs in relation to biochemical markers of inflammation was subject to study. Results. The most significant endothelioprotective activity, manifested by a decrease in the coefficient of endothelial dysfunction, had atorvastatin, L - arginine and the combination of L - arginine + nanorosuvastatin. Modeling of endotoxin - induced endothelial dysfunction led to a significant increase in the coefficient of endothelial dysfunction and NO metabolites against the background of an increase in inflammation markers C - reactive protein, IL - 6 and TNF - α. A significant decrease in biochemical markers of inflammation was observed with the use of all groups of drugs and was most effective when using statins in combination with L - arginine. Conclusion. The most pronounced positive effect on endothelial function was observed with the use of nanorosuvastatin and the combination of nanorosuvastatin + darbepoetin. L - arginine and its combination with statins demonstrated the most effective effect on biochemical markers of inflammation.