The study of the endothelial protective properties of the L-norvaline combination with mexidol in the simulation of L-NAME-induced NO deficiency

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.