National Heart, Lung, and Blood Institute Working Group Report on Salt in Human Health and Sickness

Oh, Young S.; Appel, Lawrence J.; Galis, Zorina S.; Hafler, David A.; He, Jiang; Hernandez, Amanda; Joe, Bina; Karumanchi, S. Ananth; Maric‐Bilkan, Christine; Mattson, David L.; Mehta, Nehal N.; Randolph, Gwendolyn; Ryan, Michael J.; Sandberg, Kathryn; Titze, Jens; Tolunay, Eser; Toney, Glenn M.; Harrison, David G.

doi:10.1161/hypertensionaha.116.07415

Cited by 49 publications

(39 citation statements)

References 71 publications

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“…It has long been known that HSD leads to alterations in endothelial function of cerebral and systemic vessels resulting from a reduction in endothelial NO 11 . However, most studies focused on salt-induced hypertension 8 , and it has remained unclear how long-term dietary salt intake altered cerebrovascular regulation and brain function independently of blood pressure. Using a chronic model of HSD, mimicking sustained high salt intake in humans, we found a marked reduction in resting CBF in cortex and hippocampus, associated with a selective deficit in the endothelial regulation of CBF.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical trials did not unequivocally show a health benefit from these interventions, raising questions about the scientific evidence supporting indiscriminate salt curbing in the general population 6 , 7 . Consequently, there has been a longstanding controversy about the validity of restricting sodium intake and a call for additional research to gain a better understanding in its effects in health and disease 8 .…”

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confidence: 99%

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Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response

et al. 2018

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A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia, but it remains unclear how dietary salt harms the brain. We report that, in mice, excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment. The effect depends on expansion of TH17 cells in the small intestine, resulting in a marked increase in plasma interleukin-17 (IL-17). Circulating IL-17, in turn, promotes endothelial dysfunction and cognitive impairment by the Rho kinase-dependent inhibitory phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide production in cerebral endothelial cells. The findings reveal a new gut-brain axis linking dietary habits to cognitive impairment through a gut-initiated adaptive immune response compromising brain function via circulating IL-17. Thus, the TH17 cell-IL-17 pathway is a putative target to counter the deleterious brain effects induced by dietary salt and other diseases associated with TH17 polarization.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response

et al. 2018

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“…Elevated dietary salt intake is a major contributor to the pathogenesis of cardiovascular disease (Appel et al, 2011; Kotchen et al, 2013; Oh et al, 2016). Interestingly, accumulating evidence indicates that the adverse effects of excess dietary salt on cardiovascular function may be independent of changes in arterial blood pressure (ABP) (Frohlich, 2007; Stocker et al, 2010; Appel et al, 2011; Kotchen et al, 2013; Cook et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

High Salt Intake Augments Excitability of PVN Neurons in Rats: Role of the Endoplasmic Reticulum Ca2+ Store

et al. 2017

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High salt (HS) intake sensitizes central autonomic circuitry leading to sympathoexcitation. However, its underlying mechanisms are not fully understood. We hypothesized that inhibition of PVN endoplasmic reticulum (ER) Ca2+ store function would augment PVN neuronal excitability and sympathetic nerve activity (SNA). We further hypothesized that a 2% (NaCl) HS diet for 5 weeks would reduce ER Ca2+ store function and increase excitability of PVN neurons with axon projections to the rostral ventrolateral medulla (PVN-RVLM) identified by retrograde label. PVN microinjection of the ER Ca2+ ATPase inhibitor thapsigargin (TG) increased SNA and mean arterial pressure (MAP) in a dose-dependent manner in rats with a normal salt (NS) diet (0.4%NaCl). In contrast, sympathoexcitatory responses to PVN TG were significantly (p < 0.05) blunted in HS treated rats compared to NS treatment. In whole cell current-clamp recordings from PVN-RVLM neurons, graded current injections evoked graded increases in spike frequency. Maximum discharge was significantly augmented (p < 0.05) by HS diet compared to NS group. Bath application of TG (0.5 μM) increased excitability of PVN-RVLM neurons in NS (p < 0.05), yet had no significant effect in HS rats. Our data indicate that HS intake augments excitability of PVN-RVLM neurons. Inhibition of the ER Ca2+-ATPase and depletion of Ca2+ store likely plays a role in increasing PVN neuronal excitability, which may underlie the mechanisms of sympathoexcitation in rats with chronic HS intake.

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“…We support continued exploration of these social determinants and conditions, especially obesity, sedentary lifestyle, sleep disordered breathing, and dietary factors such as higher sodium intake 6 and lower potassium intake.…”

Section: Introductionmentioning

confidence: 58%

Building on a Legacy of Hypertension Research

et al. 2017

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National Heart, Lung, and Blood Institute Working Group Report on Salt in Human Health and Sickness

Cited by 49 publications

References 71 publications

Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response

Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response

High Salt Intake Augments Excitability of PVN Neurons in Rats: Role of the Endoplasmic Reticulum Ca2+ Store

Building on a Legacy of Hypertension Research

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