Apocynin and tempol ameliorate dietary sodium-induced declines in cutaneous microvascular function in salt-resistant humans

Meghan G. Ramick, Michael S. Brian, Evan Matthews, Jordan C. Patik, Douglas R. Seals, Shannon L. Lennon, William B. Farquhar, David G. Edwards

Research output: Contribution to journalArticle

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Abstract

It has previously been shown that high dietary salt impairs vascular function independent of changes in blood pressure. Rodent studies suggest that NADPH-derived reactive oxygen species mediate the deleterious effect of high salt on the vasculature, and here we translate these findings to humans. Twenty-nine healthy adults (34 ± 2 yr) participated in a controlled feeding study. Participants completed 7 days of a low-sodium diet (LS; 20 mmol sodium/day) and 7 days of a high-sodium diet (HS; 300 mmol sodium/day) in random order. All participants were salt resistant, defined as a ≤5-mmHg change in 24-h mean BP determined while on the LS and HS diets. Laser Doppler flowmetry was used to assess cutaneous vasodilation in response to local heating (42°C) during local delivery of Ringer’s (n > 29), 20 mM ascorbic acid (AA; n > 29), 10 μM Tempol (n > 22), and 100 μM apocynin (n > 22). Additionally, endothelial cells were obtained in a subset of participants from an antecubital vein and stained for nitrotyrosine (n > 14). Cutaneous vasodilation was attenuated by the HS diet compared with LS [LS 93.0 ± 2.2 vs. HS 86.8 ± 2.0 percentage of maximal cutaneous vascular conductance (%CVCmax); P < 0.05] and was restored by AA during the HS diet (AA 90.7 ± 1.2 %CVCmax; P < 0.05 vs. HS). Cutaneous vasodilation was also restored with the local infusion of both apocynin (P < 0.01) and Tempol (P < 0.05) on the HS diet. Nitrotyrosine expression was increased on the HS diet compared with LS (P < 0.05). These findings provide direct evidence of dietary sodium-induced endothelial cell oxidative stress and suggest that NADPH-derived reactive oxygen species contribute to sodium-induced declines in microvascular function. NEW & NOTEWORTHY High-sodium diets have deleterious effects on vascular function, likely mediating, in part, the increased cardiovascular risk associated with a high sodium intake. Local infusion of apocynin and Tempol improved microvascular function in salt-resistant adults on a high-salt diet, providing evidence that reactive oxygen species contribute to impairments in microvascular function from high salt. This study provides insight into the blood pressure-independent mechanisms by which dietary sodium impairs vascular function.

Original languageEnglish
Pages (from-to)H97-H103
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume317
Issue number1
DOIs
StatePublished - 1 Jan 2019

Fingerprint

Dietary Sodium
Salts
Diet
Skin
Sodium
Blood Vessels
Vasodilation
Reactive Oxygen Species
NADP
Endothelial Cells
Blood Pressure
Sodium-Restricted Diet
Laser-Doppler Flowmetry
acetovanillone
tempol
Heating
Ascorbic Acid
Veins
Rodentia
Oxidative Stress

Keywords

  • Cutaneous vasodilation
  • Nitric oxide
  • Oxidative stress
  • Sodium

Cite this

Ramick, Meghan G. ; Brian, Michael S. ; Matthews, Evan ; Patik, Jordan C. ; Seals, Douglas R. ; Lennon, Shannon L. ; Farquhar, William B. ; Edwards, David G. / Apocynin and tempol ameliorate dietary sodium-induced declines in cutaneous microvascular function in salt-resistant humans. In: American Journal of Physiology - Heart and Circulatory Physiology. 2019 ; Vol. 317, No. 1. pp. H97-H103.
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Apocynin and tempol ameliorate dietary sodium-induced declines in cutaneous microvascular function in salt-resistant humans. / Ramick, Meghan G.; Brian, Michael S.; Matthews, Evan; Patik, Jordan C.; Seals, Douglas R.; Lennon, Shannon L.; Farquhar, William B.; Edwards, David G.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 317, No. 1, 01.01.2019, p. H97-H103.

Research output: Contribution to journalArticle

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T1 - Apocynin and tempol ameliorate dietary sodium-induced declines in cutaneous microvascular function in salt-resistant humans

AU - Ramick, Meghan G.

AU - Brian, Michael S.

AU - Matthews, Evan

AU - Patik, Jordan C.

AU - Seals, Douglas R.

AU - Lennon, Shannon L.

AU - Farquhar, William B.

AU - Edwards, David G.

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N2 - It has previously been shown that high dietary salt impairs vascular function independent of changes in blood pressure. Rodent studies suggest that NADPH-derived reactive oxygen species mediate the deleterious effect of high salt on the vasculature, and here we translate these findings to humans. Twenty-nine healthy adults (34 ± 2 yr) participated in a controlled feeding study. Participants completed 7 days of a low-sodium diet (LS; 20 mmol sodium/day) and 7 days of a high-sodium diet (HS; 300 mmol sodium/day) in random order. All participants were salt resistant, defined as a ≤5-mmHg change in 24-h mean BP determined while on the LS and HS diets. Laser Doppler flowmetry was used to assess cutaneous vasodilation in response to local heating (42°C) during local delivery of Ringer’s (n > 29), 20 mM ascorbic acid (AA; n > 29), 10 μM Tempol (n > 22), and 100 μM apocynin (n > 22). Additionally, endothelial cells were obtained in a subset of participants from an antecubital vein and stained for nitrotyrosine (n > 14). Cutaneous vasodilation was attenuated by the HS diet compared with LS [LS 93.0 ± 2.2 vs. HS 86.8 ± 2.0 percentage of maximal cutaneous vascular conductance (%CVCmax); P < 0.05] and was restored by AA during the HS diet (AA 90.7 ± 1.2 %CVCmax; P < 0.05 vs. HS). Cutaneous vasodilation was also restored with the local infusion of both apocynin (P < 0.01) and Tempol (P < 0.05) on the HS diet. Nitrotyrosine expression was increased on the HS diet compared with LS (P < 0.05). These findings provide direct evidence of dietary sodium-induced endothelial cell oxidative stress and suggest that NADPH-derived reactive oxygen species contribute to sodium-induced declines in microvascular function. NEW & NOTEWORTHY High-sodium diets have deleterious effects on vascular function, likely mediating, in part, the increased cardiovascular risk associated with a high sodium intake. Local infusion of apocynin and Tempol improved microvascular function in salt-resistant adults on a high-salt diet, providing evidence that reactive oxygen species contribute to impairments in microvascular function from high salt. This study provides insight into the blood pressure-independent mechanisms by which dietary sodium impairs vascular function.

AB - It has previously been shown that high dietary salt impairs vascular function independent of changes in blood pressure. Rodent studies suggest that NADPH-derived reactive oxygen species mediate the deleterious effect of high salt on the vasculature, and here we translate these findings to humans. Twenty-nine healthy adults (34 ± 2 yr) participated in a controlled feeding study. Participants completed 7 days of a low-sodium diet (LS; 20 mmol sodium/day) and 7 days of a high-sodium diet (HS; 300 mmol sodium/day) in random order. All participants were salt resistant, defined as a ≤5-mmHg change in 24-h mean BP determined while on the LS and HS diets. Laser Doppler flowmetry was used to assess cutaneous vasodilation in response to local heating (42°C) during local delivery of Ringer’s (n > 29), 20 mM ascorbic acid (AA; n > 29), 10 μM Tempol (n > 22), and 100 μM apocynin (n > 22). Additionally, endothelial cells were obtained in a subset of participants from an antecubital vein and stained for nitrotyrosine (n > 14). Cutaneous vasodilation was attenuated by the HS diet compared with LS [LS 93.0 ± 2.2 vs. HS 86.8 ± 2.0 percentage of maximal cutaneous vascular conductance (%CVCmax); P < 0.05] and was restored by AA during the HS diet (AA 90.7 ± 1.2 %CVCmax; P < 0.05 vs. HS). Cutaneous vasodilation was also restored with the local infusion of both apocynin (P < 0.01) and Tempol (P < 0.05) on the HS diet. Nitrotyrosine expression was increased on the HS diet compared with LS (P < 0.05). These findings provide direct evidence of dietary sodium-induced endothelial cell oxidative stress and suggest that NADPH-derived reactive oxygen species contribute to sodium-induced declines in microvascular function. NEW & NOTEWORTHY High-sodium diets have deleterious effects on vascular function, likely mediating, in part, the increased cardiovascular risk associated with a high sodium intake. Local infusion of apocynin and Tempol improved microvascular function in salt-resistant adults on a high-salt diet, providing evidence that reactive oxygen species contribute to impairments in microvascular function from high salt. This study provides insight into the blood pressure-independent mechanisms by which dietary sodium impairs vascular function.

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