Folic acid treatment normalizes NOS-dependence of vascular tone in the metabolic syndrome

Schneider, M.P., Schlaich, M.P., Harazny, J.M., Raff, U., Ritt, M., Ott, C. and Schmieder, R.E. (2010) Folic acid treatment normalizes NOS-dependence of vascular tone in the metabolic syndrome. Obesity, 19(5), pp. 960-967. (doi: 10.1038/oby.2010.210)

Abstract

Obese subjects with the metabolic syndrome (MS+) are more prone to microvascular complications than obese subjects without the metabolic syndrome (MS-). Excessive vascular nitric oxide (NO) production has been demonstrated in MS+ compared to MS-, perhaps driven by increased inflammation or oxidative stress. We tested whether in MS+, folic acid (FA) treatment could normalize NO synthase (NOS)- dependence of vascular tone in the retina and kidney. MS+ (n = 49) and MS- (n = 26) subjects were included in a randomized, double-blind, crossover trial. After 4- weeks' treatment with placebo or FA (5 mg/day), several cytokines (C-reactive protein (CRP), interleukin-1 beta, adiponectin), and markers of oxidative stress (glutathione/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (TAC)) were determined. NOS-dependence of retinal and renal vascular tone was assessed by retinal scanning laser Doppler flowmetry and renal clearance technique, respectively. FA had no effect on cytokine levels, but increased GSH/GSSG ratio overall (36 +/- 76 vs. 102 +/- 200, P = 0.04), indicative of a reduction in oxidative stress. In MS+, treatment with FA reduced NOS-dependence of retinal and renal vascular tone compared to placebo (P = 0.03 and P = 0.04, respectively). FA had no effect in MS-. After treatment with FA, NOS-dependence of retinal and renal vascular tone was similar between MS+ and MS-. Retinal and renal vascular tone in MS+ subjects is characterized by increased dependence on NOS. NOS-dependence in MS+ could be corrected by FA treatment to levels not dissimilar in MS-, and this was associated with a reduction in oxidative stress. Future trials should test whether these effects translate into a reduction of microvascular complications.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Schneider, Dr Markus
• Authors: Schneider, M.P., Schlaich, M.P., Harazny, J.M., Raff, U., Ritt, M., Ott, C., and Schmieder, R.E.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Obesity
• ISSN: 1930-7381