Pharmacological correction of endothelial dysfunction using a complex of grape polyphenols

Аннотация

Introduction: Endothelial dysfunction is an important component of cardiovascular disease pathogenesis. Natural polyphenols are of interest as potential endothelioprotective agents. The aim of this study was to evaluate the endothelioprotective activity of a grape polyphenol complex in a mouse model of endothelial dysfunction.

Materials and Methods: The study was performed on 50 male C57BL/6 mice. Endothelial dysfunction was induced by administration of L-NAME in drinking water (0.5 mg/mL) for 4 weeks. The animals were divided into five groups (n = 10): intact, control(L-NAME), L-NAME + resveratrol, L-NAME + atorvastatin, and L-NAME + grape polyphenol complex. The estimated daily intake per animal was 0.812 mg of resveratrol, 0.052 mg of atorvastatin, and 0.08 mL of the grape polyphenol complex. Systolic and diastolic blood pressure and endothelium-dependent vascular responses were assessed by invasive hemodynamic monitoring.  Morphometric analysis of the heart and kidneys was performed. Edn1, Nos3, and Vegfa expression was evaluated by real-time quantitative PCR.

Results and Discussion: The grape polyphenol complex reduced systolic and diastolic blood pressure and the endothelial dysfunction coefficient compared with the L-NAME control. It also reduced morphological changes in the heart and kidneys, increased Nos3 expression, and decreased Edn1 and Vegfa expression. The observed changes approached the values of intact animals and indicate restoration of NO-dependent endothelial regulation.

Conclusion: Administration of the grape polyphenol complex at 0.08 mL/day for 4 weeks produced an endothelioprotective effect in C57BL/6 mice with L-NAME-induced endothelial dysfunction. Treatment improved endothelium-dependent vascular responses, systemic hemodynamics, tissue morphology, and endothelial-related gene expression.

Графическая аннотация