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Folic Acid Treatment Normalizes NOS‐Dependence of Vascular Tone in the Metabolic Syndrome
Author(s) -
Schneider Markus P.,
Schlaich Markus P.,
Harazny Joanna M.,
Raff Ulrike,
Ritt Martin,
Ott Christian,
Schmieder Roland E.
Publication year - 2011
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2010.210
Subject(s) - medicine , oxidative stress , endocrinology , retinal , adiponectin , nitric oxide synthase , placebo , nitric oxide , metabolic syndrome , glutathione , chemistry , pathology , biochemistry , insulin resistance , ophthalmology , enzyme , alternative medicine , insulin , obesity
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‐1β, 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.