Correction of morphofunctional disorders of the cardiovascular system with asialized erythropoietin and arginase II selective inhibitors KUD 974 and KUD 259 in experimental preeclampsia

Abstract

Introduction: Preeclampsia remains one of the most common causes of maternal and perinatal mortality worldwide. A significant role in the pathogenesis of this pathology is assigned to placental ischemia and endothelial dysfunction. Therefore, the aim of the present study was to study the effectiveness of asialized erythropoietin and arginase II selective inhibitors: KUD-259 and KUD-974 in the correction of morphofunctional disorders of the cardiovascular system in experimental preeclampsia. Materials and methods: The study was performed in 260 female Wistar rats, each weighing 250–300 g. An ADMA-like preeclampsia was reproduced in the experiment. To assess the emerging morphofunctional disorders, the following parameters were used: blood pressure, coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid content in the omentum, concentration of terminal metabolites in the blood plasma, and morphometric parameters of fetuses. Results and discussion: The administration of arginase II selective inhibitor KUD-974 in combination with asialized erythropoietin leads to a pronounced correction of emerging changes: a decrease in systolic and diastolic blood pressure in 1.5 and 1.7 times, a decrease in proteinuria in 3.6 times and a decrease in fluid content in the omentum. When arginase II selective inhibitor KUD 974 and asialized erythropoietin are used with methyldopa, the positive effects of the former are enhanced. Conclusion: Arginase II selective inhibitors KUD-259 and KUD-974 and asialized erythropoietin have a pronounced positive effect on the correction of morphofunctional disorders in animals with ADMA-like preeclampsia.