Abstract
Introduction: The endothelium is considered as a target for the prevention and treatment of pathological processes leading to cardiovascular diseases.
 Materials and methods: Endothelial dysfunction was simulated in male rats using an e-NOS inhibitor L-NAME (25 mg/kg/day intraperitoneally, 7 days). This pathology was then corrected by administering mexidol at a dose of 60 mg/kg and L-norvaline at a dose of 10 mg/kg, as well as the combination of both at the same doses, intragastrically, through an atraumatic probe, once a day.
 Results and discussion: A combination of L-norvaline at a dose of 10 mg/kg and mexidol at a dose of 60 mg/kg against the background of L-NAME-induced endothelial dysfunction has a pronounced endothelial protective effect. This is reflected in the prevalence of endothelial-dependent vascular relaxation, a significant decrease in the coefficient of endothelial dysfunction, as well as the prevention of a decline in the concentrations of stable nitric oxide metabolites and of a decrease in the level of the inflammatory changes marker in the vascular wall. The combination of L-norvaline and mexidol, with different pathogenetic action mechanisms, has a pronounced endothelial protective effect because of their antioxidant properties (mexidol) and donation of nitric oxide (L-arginine).
 Conclusion: The investigated drugs showed pronounced endothelial protective activity and can be recommended for further pre-clinical studies.
Highlights
The endothelium is considered as a target for the prevention and treatment of pathological processes leading to cardiovascular diseases
The values of indicators of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the group of intact animals were considered as the target values of blood pressure
The experiment revealed that the combined use of L-norvaline and mexidol, in contrast to monotherapies with these drugs, had a hypotensive effect, which was significantly different from that in the animals treated with monotherapies with these substances against the background of L-NAME
Summary
The endothelium is considered as a target for the prevention and treatment of pathological processes leading to cardiovascular diseases. Materials and methods: Endothelial dysfunction was simulated in male rats using an e-NOS inhibitor L-NAME (25 mg/kg/day intraperitoneally, 7 days) This pathology was corrected by administering mexidol at a dose of 60 mg/kg and L-norvaline at a dose of 10 mg/kg, as well as the combination of both at the same doses, intragastrically, through an atraumatic probe, once a day. Results and discussion: A combination of L-norvaline at a dose of 10 mg/kg and mexidol at a dose of 60 mg/kg against the background of L-NAME-induced endothelial dysfunction has a pronounced endothelial protective effect This is reflected in the prevalence of endothelial-dependent vascular relaxation, a significant decrease in the coefficient of endothelial dysfunction, as well as the prevention of a decline in the concentrations of stable nitric oxide metabolites and of a decrease in the level of the inflammatory changes marker in the vascular wall. The barrier role of the vascular endothelium as an active organ determines its main role in the human body: maintaining homeostasis by regulating the equilibrium state of opposite processes – vascular tone (vasodilation/ vasoconstriction), anatomical structure of the vessels (synthesis/inhibition of proliferation factors), hemostasis (synthesis and inhibition of fibrinolysis factors and of platelet aggregation), and local inflammation (production of pro- and anti-inflammatory factors)
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