Grape seed flavanols decrease blood pressure via Sirt-1 and confer a vasoprotective pattern in rats

• Sirtuin-1 mediates the antihypertensive effect of grape seed flavanols.
• Grape seed flavanols upregulate aortic eNOS and Sirt-1 gene expression.
• Grape seed flavanols downregulate aortic NOX4 and ET-1 gene expression and plasma ET-1 levels.
• Grape seed flavanols improve endothelial pattern.

Involvement of nitric oxide (NO) in the antihypertensive effect of grape seed flavanols was previously demonstrated. This study investigates the endothelial vasoprotective pattern and the role of Sirtuin-1 (Sirt-1) in this antihypertensive effect. Cafeteria diet-fed hypertensive rats (CHR) were administered water or 375 mg/kg of a low-molecular grape seed polyphenol extract (LM-GSPE) rich in flavanols and sacrificed 6 h post-administration. Plasma endothelin-1 (ET-1) and aortic expression of NO pathway genes, NADPH oxidase subunit 4 (NOX4) and ET-1 genes were measured. LM-GPSE decreased plasma ET-1, upregulating eNOS and Sirt-1 and downregulating aortic gene expression of ET-1 and NADPH, the endothelial major producer of free radicals, indicating the vasoprotective effect of grape seed flavanols. Additionally, twenty-four spontaneously hypertensive rats (SHR) were administered water or 375 mg/kg LM-GSPE and treated with 1 mg/kg sirtinol (inhibitor of Sirt-1). The antihypertensive effect of LM-GSPE was completely abolished by sirtinol, indicating that grape seed flavanols decrease BP in a Sirt-1-dependent manner.