Sodium nitrate supplementation improves blood pressure reactivity in patients with peripheral artery disease

doi:10.1016/j.numecd.2021.12.002

Nutrition, Metabolism and Cardiovascular Diseases

Volume 32, Issue 3, March 2022, Pages 710-714

https://doi.org/10.1016/j.numecd.2021.12.002 Get rights and content

Highlights

•
PAD is associated with exaggerated blood pressure responses.
•
Patients with PAD have low nitric oxide (NO) availability.
•
Inorganic nitrate reduces blood pressure and increases NO in healthy individuals.
•
8 weeks of inorganic nitrate in PAD patients reduces BP responses to a cold stress.

Abstract

Background & aims

Peripheral artery disease (PAD) is characterized by elevated blood pressure (BP), low nitric oxide availability (NO), and exaggerated pressor responses to sympatho-excitatory stressors. Inorganic nitrate reduces peripheral BP in healthy and chronically diseased populations. The objective of this study was to investigate the effects of eight-weeks of sodium nitrate (NaNO₃) supplementation on indices of BP in PAD patients.

Methods

21 patients with PAD were recruited to participate in this study, undergoing 8-weeks of NaNO₃ (n = 13; 73 ± 9 years) or placebo (n = 8; 69 ± 10 years) supplementation. BP responsiveness to a cold pressor test (CPT) were examined prior to and following the supplementation period. The systolic BP response (change from rest) during the first (26 ± 10 vs. 19 ± 11 mmHg) and second minutes (32 ± 10 vs. 26 ± 12 mmHg) of CPT were reduced following NaNO₃ (P < 0.05 for both) but not after placebo (first minute: 22 ± 10 vs. 24 ± 10 mmHg, P = 0.30; second minute 26 ± 10 vs 27 ± 10 mmHg, P = 0.72) supplementation.

Conclusion

Our data suggest that eight-weeks of NaNO₃ supplementation reduces BP responsiveness to sympatho-excitatory stimuli.

Clinical trials registration number

NCT01983826.

Introduction

Peripheral arterial disease (PAD), characterized by systemic atherosclerosis, is associated with elevated blood pressure (BP), and low nitric oxide (NO) bioavailability [[1], [2], [3]]. Adequate BP management is crucial in these patients to reduce the risk of major adverse cardiovascular events (MACE) [4,5]. While static (in-office/clinic) BP is used to diagnose hypertension, BP responsiveness to physiological or psychological stressors are stronger predictors of future hypertension [[6], [7], [8], [9], [10]].

Supplementation with inorganic nitrate ${NO}_{3}^{-}$ effectively reduces clinic/office BP [11,12]. BP reduction via inorganic ${NO}_{3}^{-}$ presents a new avenue in the management of BP in subjects with PAD. It is unclear whether inorganic ${NO}_{3}^{-}$ supplementation improves BP responsiveness in patients with PAD. We hypothesized that NaNO₃ supplementation would minimize the exaggerated BP response to sympatho-excitatory stimuli.

Section snippets

Study population

Twenty-one patients with PAD participated in the study. Inclusion criteria were clinically diagnosed PAD and the ability to walk without severe leg symptoms. Exclusion criteria included non-atherosclerotic vascular disease, critical limb ischemia, active ischemic ulceration, recent (within six months) revascularization, symptomatic coronary artery disease, heart failure, renal disease, hypotension (resting systolic BP < 90 mmHg), smoking or history of smoking within one year, and the use of

Results

Table 1 illustrates subject characteristics, comorbidities, and drug regimens within the placebo and NaNO₃ groups, along with brachial BP prior to supplementation in either group. Eight weeks of NaNO₃ supplementation effectively elevated plasma [ ${NO}_{3}^{-}$ ] and [ ${NO}_{2}^{-}$ ] compared to placebo, as we have previously reported [13].

Discussion

This study examined the effects of eight weeks of NaNO₃ supplementation on BP responsiveness in patients with PAD. Previously, we reported improvements in resting brachial SBP, but not brachial DBP or MAP in this same PAD cohort following eight weeks of NaNO₃ [13,14]. Within the current study, NaNO₃ supplementation improved systolic BP responsiveness to sympatho-excitatory stimuli (CPT) in patients with PAD (Fig. 1).

Conclusion

This study sought to examine the effects of eight weeks of supplementation with NaNO₃ on BP responsiveness in patients with PAD. Eight weeks of NaNO₃ supplementation reduces systolic BP responsiveness to sympatho-excitatory stimuli. Taken together, these results suggest that while NaNO₃ supplementation may have positive benefits on BP, these effects are not universally observed across various indices of BP in patients with PAD.

Declaration of competing interest

The authors have no competing interests or conflicts to report.

Acknowledgements

This work was supported by the American Heart Association [13GRNT16490002, DPC] and National Institutes of Health Clinical and Translational Science Award [U54TR001356].

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There are more references available in the full text version of this article.

Cited by (2)

Reduction in blood pressure following acute dietary nitrate ingestion is correlated with increased red blood cell S-nitrosothiol concentrations
2023, Nitric Oxide - Biology and Chemistry
Dietary nitrate (NO₃⁻) supplementation can enhance nitric oxide (NO) bioavailability and lower blood pressure (BP) in humans. The nitrite concentration ([NO₂⁻]) in the plasma is the most commonly used biomarker of increased NO availability. However, it is unknown to what extent changes in other NO congeners, such as S-nitrosothiols (RSNOs), and in other blood components, such as red blood cells (RBC), also contribute to the BP lowering effects of dietary NO₃⁻. We investigated the correlations between changes in NO biomarkers in different blood compartments and changes in BP variables following acute NO₃⁻ ingestion. Resting BP was measured and blood samples were collected at baseline, and at 1, 2, 3, 4 and 24 h following acute beetroot juice (∼12.8 mmol NO₃⁻, ∼11 mg NO₃⁻/kg) ingestion in 20 healthy volunteers. Spearman rank correlation coefficients were determined between the peak individual increases in NO biomarkers (NO₃⁻, NO₂⁻, RSNOs) in plasma, RBC and whole blood, and corresponding decreases in resting BP variables. No significant correlation was observed between increased plasma [NO₂⁻] and reduced BP, but increased RBC [NO₂⁻] was correlated with decreased systolic BP (r_s = −0.50, P = 0.03). Notably, increased RBC [RSNOs] was significantly correlated with decreases in systolic (r_s = −0.68, P = 0.001), diastolic (r_s = −0.59, P = 0.008) and mean arterial pressure (r_s = −0.64, P = 0.003). Fisher's z transformation indicated no difference in the strength of the correlations between increases in RBC [NO₂⁻] or [RSNOs] and decreased systolic blood pressure. In conclusion, increased RBC [RSNOs] may be an important mediator of the reduction in resting BP observed following dietary NO₃⁻ supplementation.
Antioxidant Capacity, Nitrite and Nitrate Content in Beetroot-Based Dietary Supplements
2023, Foods

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© 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Short CommunicationSodium nitrate supplementation improves blood pressure reactivity in patients with peripheral artery disease

Highlights

Abstract

Background & aims

Methods

Conclusion

Clinical trials registration number

Introduction

Section snippets

Study population

Results

Discussion

Conclusion

Declaration of competing interest

Acknowledgements

J Sci Med Sport

J Nutr

Nitric Oxide : Biol Chem/Off J Nitric Oxide Soc

Free Radic Biol Med

Nitric oxide: link between endothelial dysfunction and inflammation in patients with peripheral arterial disease of the lower limbs

Interact Cardiovasc Thorac Surg

Peripheral artery disease: epidemiology and global perspectives

Nat Rev Cardiol

Differential contribution of endothelium-derived relaxing factors to vascular reactivity in conduit and resistance arteries from normotensive and hypertensive rats

Clin Exp Hypertens (New York, NY: 1993)

Hypertension in peripheral arterial disease

Curr Pharmaceut Des

Association of hypertension and arterial blood pressure on limb and cardiovascular outcomes in symptomatic peripheral artery disease: the EUCLID trial

Circ Cardiovasc Qual outcomes

Short Communication
Sodium nitrate supplementation improves blood pressure reactivity in patients with peripheral artery disease