Ascorbic acid lowers central blood pressure and asymmetric dimethylarginine in chronic kidney disease

Abstract

Background: Premature cardiovascular disease in patients with chronic kidney disease (CKD) is not explained by traditional risk factors and oxidative stress may contribute via endothelial and vascular dysfunction. We investigated the effect of ascorbic acid on oxidative stress and vascular function in CKD patients compared with controls with hypertension (HTN).

Methods: A crossover study of intravenous saline and ascorbic acid was conducted. Biomarkers of oxidative stress were measured, while pulse wave analysis and brachial flow-mediated dilatation were performed to assess large artery and endothelial function.

Results: Twenty HTN and 30 CKD patients Stages 3-5 were recruited. Serum ascorbic acid was significantly lower in patients with CKD. In both groups, ascorbic acid significantly increased total antioxidant potential and superoxide. Asymmetric dimethylarginine (ADMA) was reduced significantly by ascorbic acid in the CKD group and on multivariate regression analysis, age and the presence of CKD were predictors of ADMA response to ascorbic acid. Although no effect on FMD was observed, central blood pressure and augmentation index were reduced significantly in both groups.

Conclusions: Ascorbic acid has pro- and antioxidant effects, reducing central blood pressure and augmentation index in HTN and CKD. Ascorbic acid reduces serum ADMA in CKD, which may have longer-term benefits.

Keywords: antioxidants; arterial stiffness; chronic kidney disease; endothelial dysfunction; oxidative stress.

Fig. 1.

Change in (A) ascorbic acid, (B) ${\mathrm{O}}_2^{\text{−}}$ production, (C) ADMA and (D) TAP in both groups after administration of ascorbic acid. Measurements of biomarkers of oxidative stress made in both groups are shown at (1) baseline, (2) after ascorbic acid and (3) at 1 h after ascorbic acid. *Indicates a significant difference (P < 0.05) in comparison with baseline.

Fig. 2.

Change in (A) central BP and (B) Aix in both HTN and CKD. *Indicate a significant difference (P < 0.05) occurring after ascorbic acid. SAL, normal saline; AA, ascorbic acid; NS, not significant.