Корекція функції ендотелію - нова ціль профілактики і лікування артеріальної гіпертензії в пацієнтів із серцево-судинною патологією

Abstract

Purpose - to determine the dynamics of endothelial progenitor cells (EPCs) and asymmetric dimethylarginine (ADMA) in pregnant women with hypertension as markers of the effectiveness of endothelial dysfunction correction on the background of L-arginine therapy (Tivortin, manufactured by Yuria-Pharm). Materials and methods. The study pregnant women were divided into two groups: women with hypertension at 12-15 weeks of gestation (n=29) and women with congenital heart disease at 12-14 weeks of gestation (n=21). The control group consisted of 40 healthy pregnant women. The examination was conducted before the start of oral L-arginine (Tivortin aspartate) and 7-8 weeks after the start of therapy. Tivortin aspartate was administered orally 1 measuring spoon 5 times a day for 6 weeks. The study of the level of EPCs (CD45+/CD34+ phenotype of peripheral blood) was performed by flow cytometry using reagents for the determination of CD34, CD45 differentiation clusters produced by Beckman Coulter Inc. The results are presented in % of ERC from the total number of leukocytes, as well as in absolute values - the number of cells per 1 ml of blood in absolute values. The level of ADMA in plasma was determined by an indirect enzyme-linked immunosorbent assay using the ADMA ELISA test system (manufactured by Immunodiagnostik AG, Germany). The reference values for pregnant women are 0.26-0.60 μmol/l. Results. After treatment with L-arginine (Tivortin), the ADMA index decreased compared to baseline data in the studied groups of pregnant women. Thus, in pregnant women with hypertension, ADMA decreased by almost 15%, which is a marker of improved endothelial function. The same dynamics was observed in the group of women with congenital heart disease. In both study groups of pregnant women, the number of EPCs increased by almost 10% after the addition of L-arginine (Tivortin) to the treatment complex. There was a positive correlation between a decrease in mean systolic blood pressure, an increase in EPCs and a decrease in ADMA after complex treatment. Studies have shown a direct correlation (r=0.75) between blood pressure and the number of ЕРСs and an inverse correlation (r=-0.68) between blood pressure and ADMA. The reduction in blood pressure during treatment was accompanied by an improvement in endothelial function, namely, an increase in the number of ЕРСs, mainly due to the vasodilation potential of the endothelium. There was also a decrease in ADMA against the background of a decrease in systolic blood pressure during treatment. Conclusions. The clinical relevance of asymmetric dimethylarginine as a specific marker in patients with hypertension has been established: a significant increase in its level is observed in patients with cardiovascular disease, in particular, with hypertension, which confirms the role of endothelial dysfunction as a leading pathogenetic factor in the development of hypertension in the absence of anatomical and pathological changes in the vessels. The concept of maintenance therapy in patients with cardiovascular disease aims to restore adequate NO bioavailability by administering exogenous L-arginine. Based on the results of the study of the effect of L-arginine (Tivortin) on the index of ЕРСs, which are actively involved in the repair of damaged endothelium, it can be concluded that this drug has a positive effect on the prognosis of life in patients with hypertension, restoring endothelial function. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.