Abstract
Introduction: Рharmacological correction of endothelial dysfunction is a urgent problem of modern medicine.
 Materials and methods: Endothelial dysfunction was simulated in male rats using the e-NOS inhibitor L-NAME (25 mg/kg/day intraperitoneally, for 7 days). Simulation of ADMA-like preeclampsia was performed by intraperitoneal injection of L-NAME to females in the same doses for 7 days (14-20th days of pregnancy). These pathologies were corrected by administering ademethionine in dose 150 mg/kg and taurine at a dose of 260 mg/kg, as well as their combination at the same doses, intragastrically, through an atraumatic probe, once a day.
 Results: In the group with use of taurine at a dose of 260 mg/kg the coefficient of endothelial dysfunction decreased to the level of intact animals. Use of ademethionine at a dose of 150 mg/kg and taurine at a dose of 260 mg/kg combined resulted in the most pronounced endothelioprotective effect on the ADMA-like preeclampsia model. The coefficient of endothelial dysfunction decreased more than when using monotherapy of these drugs. Morphological studies of myocardiocytes showed that the combination of ademethionine at a dose of 150 mg/kg and taurine at a dose of 260 mg/kg prevented an increase in the cross-section of cardiomyocytes.
 Discussion: Possibly, ademethionine and taurine have an endothelioprotective effect because of their ability to decrease hyperhomocysteinemia.
 Conclusion: The investigated drugs showed pronounced endothelioprotective activity and can be recommended for further pre-clinical studies.
Highlights
Рharmacological correction of endothelial dysfunction is a urgent problem of modern medicine
From the literature it is known that ademethionine has an endothelioprotective effect by blocking the protein arginine methyltransferase (PАMT) enzyme – an enzyme that participates in the synthesis of asymmetric dimethylarginine (ADMA), and taurine, in turn, is a powerful antioxidant: it inhibits the production of superoxide radicals, decreases the production of the factor, and decreases the tumor necrosis factor, which is a marker of placenta inflammation, and restores the expression of endothelial nitrogen oxide (NO) synthase
It should be noted that the proposed methodological complex of functional, biochemical and morphological changes linked with the development of NO deficiency due to the blockade of NO-synthase in male rats and pregnant female rats against the background of preeclampsia makes it possible to quite objectively detect and evaluate the endotheliotropic effect of pharmacological agents
Summary
Рharmacological correction of endothelial dysfunction is a urgent problem of modern medicine. Simulation of ADMA-like preeclampsia was performed by intraperitoneal injection of L-NAME to females in the same doses for 7 days (14-20th days of pregnancy). These pathologies were corrected by administering ademethionine in dose 150 mg/kg and taurine at a dose of 260 mg/kg, as well as their combination at the same doses, intragastrically, through an atraumatic probe, once a day. Results: In the group with use of taurine at a dose of 260 mg/kg the coefficient of endothelial dysfunction decreased to the level of intact animals. Use of ademethionine at a dose of 150 mg/kg and taurine at a dose of 260 mg/kg combined resulted in the most pronounced endothelioprotective effect on the ADMA-like preeclampsia model.
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