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BackgroundThe bioavailability of nitric oxide (NO) has been shown to contribute to vascular function during peak exercise. Young women with Metabolic Syndrome (MetSyn) have presented with a deficit in vascular conductance during exercise hyperemia. Since NO has been shown to play a key role in vasodilation during exercise, it is crucial to identify if there is a deficit in the NO synthesis and how it affects vasculature of these young women. The aim of this study is to measure changes in bioavailable blood NO levels at rest and during peak handgrip exercise and determine its correlation to vascular conductance in women with MetSyn compared to healthy controls.MethodsIn this study, 15 participants (6 MetSyn and 9 Controls) performed the procedure of graded handgrip exercise on a dynamic handgrip device while beat‐to‐beat blood pressure (CNAP finger plethysmography), brachial artery diameter and blood flow with Doppler ultrasound and B‐mode imaging were measured continuously. During this exercise, participants used a handgrip dynamometer at a cadence of 30 contractions/minute. Exercise workload was increased in a ramp fashion (0.5 kg·min−1) until task failure. At rest and immediately upon task failure, a venipuncture was performed to take rest and peak NO levels to be later measured by a EPR Spectroscopy and Colorimetric Nitrate/Nitrite commercial ELISA kit. Whole blood was drawn into a prepared vacutainer in a 1:1 venous blood to the metal chelator, deferoxamine (DF), in diethyldithiocarbamate (DETC) Krebs buffer. Plasma was preserved with EDTA and all samples were immediately flash frozen in liquid nitrogen and stored at −80 degrees Celsius.ResultsThere was a significant difference in resting NO values (p=0.034) as well as end NO concentration values (p=0.053) between MetSyn and control groups. However, the MetSyn showed higher resting and peak NO values than control group as measured by ELISA. The change in plasma NO did not show any significant changes from rest to peak exercise in both groups (MetSyn p=0.757, control p=0.562). However, using the EPR spectroscopy method there is a significant difference identified between rest and peak exercise (p<0.05). There was no significant change in NO between the groups (p=0.633). The MetSyn group has a significantly diminished arterial conductance in the brachial artery during handgrip as well as a attenuated response in the femoral artery during dynamic leg kick. The change in brachial conductance did not show significant correlation to the change in NO levels in either of the groups (MetSyn p=0.792, r=−0.321, control p=0.549, r=−0.310) with the ELISA method.ConclusionsThe colorimetric nitrate/nitrite ELISA assay is not a reliable technique to measure the degree of change of NO concentrations at peak exercise. The whole blood EPR technique previously used in our laboratory work showed more significant results associated with the declining exercise hyperemia of the MetSyn group. Future studies will focus on clarifying methodologies for quantifying blood NO bioavailability at peak exercise.Support or Funding InformationResearch reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103451.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

PurposeSedentary populations with obesity and metabolic syndrome (MetSyn) have presented with impaired vascular dysfunction, including vasodilation reduced 40–50%. The mechanisms of vascular endothelial dysfunction have also been associated to the bioavailability of nitric oxide levels and in metabolic compromised individuals the diminished content of endothelial NO are a prime mechanistic target for study. The present study was designed to examine the association between insulin sensitivity and endothelial dysfunction with respect to the nitric oxide eNOS pathway in MetSyn women using flow mediated dilation (FMD). We hypothesize that lower production of nitric oxide and lower Insulin Sensitivity Index (ISI) will be observed in MetSyn compared to age matched‐control patients, primarily due to mechanistic dysfunction of the eNOS pathway.MethodsIn this study, 30 participants (10 MetSyn and 20 Controls) were recruited for FMD testing and vascular changes were recorded using Doppler ultrasound with a linear vascular probe. A blood pressure cuff was placed on the upper forearm and upper calf for analysis of brachial and popliteal arteries sheer rate and reactive hyperemia. Images were continuously analyzed with Brachial Analyzer software and sheer rate calculated by digital recordings of blood velocity through with a digital auditory transducer recordings with a BIOPAC 150 system and AcqKnowlege software. Insulin sensitivity index was assessed by an oral glucose tolerance test with fasting and post‐prandal glucose measured with a glucometer and insulin measured by a Human Insulin ELISA kit (Cayman Chemical). The resting bioavailability of Nitric Oxide assessed by Nitrate/Nitrite ELISA assay and NO EPR spectroscopy measurementsResultsIn the brachial arteries there is significant differences (P<0.05) in the time and rate to peak diameter from reperfusion but not within the % Dilation or sheer rate between the MetSyn and Control sedentary groups. In the popliteal arteries there is a significant difference between the % dilation, time and rate to peak from reperfusion. We observed correlations among changes in arterial measurements, Insulin Sensitivity Index (ISI) and resting Nitric oxide concentration (NO). ISI is observed to be correlated to Peak Diameter (p=0.0943, r= 0.59) and Rate to Peak (p=0.07, r=.0628) measurements in the MetSyn group in the brachial arteries with no calculated relationship identified in the popliteal artery.ConclusionWe predict that significant deficiencies will be observed between the control and MetSyn group. These comparisons may explain the vascular mechanisms of developing deficits associated with the metabolic deficiencies and provide a target for the decline in vascular function within this sedentary population. A postulated mechanism of this endothelial dysfunction during insulin resistance begins with the decreased sensitivity of the insulin receptor preventing the effect of insulin and the AKT/PKB eNOS pathway.Support or Funding InformationResearch reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103451.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.