Elsevier

Nitric Oxide

Volume 20, Issue 4, 1 June 2009, Pages 231-237
Nitric Oxide

Plasma nitrite response and arterial reactivity differentiate vascular health and performance

https://doi.org/10.1016/j.niox.2009.01.002Get rights and content

Abstract

NO is crucial for endothelial function and vascular health. Plasma nitrite (NO2) is the main oxidation product of NO and has been shown to reflect changes in eNOS activity. We hypothesized that plasma NO2 response to physical exercise stress along with physiological endothelial function would be reduced with increasing severity of vascular disease. Subject groups were: (a) risk factors but no vascular disease (RF); (b) Type 2 diabetes with no vascular disease (DM); (c) diagnosed peripheral arterial disease (PAD); and (d) DM + PAD. Venous blood was drawn at rest and 10 min following maximal exercise. Plasma samples were analyzed by reductive chemiluminescence. Brachial diameters were imaged prior to, during and following 5 min of forearm occlusion (BAFMD). There were no differences in resting plasma NO2 or BA diameters between groups. The PAD groups had lower age adjusted BAFMD responses (p  0.05). Within group analysis revealed an increase in NO2 in the RF group (+39.3%), no change in the DM (−15.51%), and a decrease in the PAD (−44.20%) and PAD + DM (−39.95%). This was maintained after adjusting for age and VO2peak (p  0.05). ΔNO2 and BAFMD were the strongest independent predictors of VO2peak in multivariate linear regression. These findings suggest ΔNO2 discriminates severity of cardiovascular disease risk, is related to endothelial function and predicts exercise capacity.

Section snippets

Patient characteristics

All subjects were recruited from the Duke University Medical Center Cardiology-Vascular clinics and surrounding area as part of ongoing enrollment for the Angiogenesis and Mechanisms of Exercise Training in PAD (AMNESTI) clinical trial. Prior to participation all subjects signed an informed consent document approved by Duke University Medical Center Internal Review Board. All subjects were aged 40–75 years. Subjects were placed in the groups.

  • RF = greater than 2 traditional risk factors, no

Patient characteristics

There were 41 subjects in the risk factor (RF) group, 10 in the diabetes only group (DM), 29 in the PAD only group, and 9 in the DM + PAD group. The subject characteristics are summarized in Table 1. The RF group was younger, had higher fitness level, and lower resting systolic blood pressures than the other groups. As expected both the RF and DM had higher ABI measures than the two diagnosed PAD groups. There were no differences in resting diastolic blood pressures or brachial artery diameters

Discussion

The major finding of this study is that subjects with clinically diagnosed vascular disease (PAD) have significantly blunted responses in: (a) localized NO-dependant endothelial function (BAFMD), (b) the ability to increase plasma nitrite (ΔNO2), and (c) exercise tolerance (VO2peak) in comparison to those with sub-clinical disease. Additionally, these physiological (BAFMD), biochemical (ΔNO2), and physical (VO2peak) indicators of vascular health/function are interrelated. In fact, within a

Summary/conclusions

The results of this study present a unique view into the biochemistry and physiological responsiveness of the vasculature in sub-clinical and clinical disease patients. Measures of endothelial function and physical performance were all able to differentiate between subjects at risk for CVD and those with clinical disease. The ability to up regulate plasma NO2 to exercise stress was also able to differentiate between the two sub-clinical “at risk” groups. Additionally, we present evidence that

Acknowledgments

Assistance for treadmill testing and exercise training in this study was provided by staff at the Duke University Medical Center, Center for Living Campus, Durham, NC 27710.

These findings were partially supported in by the NIH Grant 5R01 HL-075752-05.

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