Dietary Salt Intake Exaggerates Sympathetic Reflexes and Increases Blood Pressure Variability in Normotensive Rats

Simmonds, Sarah; Lay, Jennifer; Stocker, Sean D.

doi:10.1161/hypertensionaha.114.03250

Cited by 83 publications

(85 citation statements)

References 42 publications

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“…The results of the present study and these speculations are compatible with previous reports that increased salt intake promotes a further decline in kidney function and the development of ESRD in patients with CKD [26,27]. Mechanisms that involve endothelial dysfunction [41], activation of the sympathetic nervous system and the renin-angiotensin system within the kidney [42][43][44][45], and the transcription of mineralocorticoid receptordependent genes [44] may also be involved in the relationship between salt intake and the development of CKD.…”

Section: Discussionsupporting

confidence: 92%

Dietary Salt Intake is a Significant Determinant of Impaired Kidney Function in the General Population

Sugiura¹,

Takase²,

Ohte³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Kidney dysfunction is an important risk factor for cardiovascular disease and end-stage renal disease. This study investigated whether dietary salt intake predicts deterioration of kidney function in the general population. Methods: In all, 12 126 subjects with a normal estimated glomerular filtration rate (eGFR ≥60 mL/min per 1.73m²) attending an annual check-up were enrolled in the study and were followed-up for a median of 1754 days; the endpoint was the development of impaired kidney function (eGFR < 60 mL/min per 1.73m²). Individual salt intake was estimated using spot urine analysis. Results: At baseline, mean (± SD) salt intake and eGFR were 10.6 ± 3.4 g/day and 80.8 ± 12.9 mL/min per 1.73m², respectively. During the follow-up period, 1384 subjects (25.2 per 1000 person-years) developed impaired kidney function. Multivariate Cox hazard regression analysis revealed salt intake as a significant predictor of the new onset of kidney impairment (hazard ratio 1.045; 95% confidence interval 1.025–1.065). Subjects were divided into two groups based on salt intake; the incidence of impaired kidney function was higher in the group with high than low salt intake (P < 0.001, log-rank test). Multivariate Cox hazard regression analysis indicated a 29% increased risk of developing impaired kidney function in the high-salt group. Multivariate linear regression analysis showed a significant correlation between salt intake and yearly decline in eGFR (β = 0.060, P < 0.001). Conclusion: Salt intake is associated with the development of impaired kidney function in the general population, independent of its effects on blood pressure. Salt restriction may help prevent the development of impaired kidney function.

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Section: Discussionsupporting

confidence: 92%

Dietary Salt Intake is a Significant Determinant of Impaired Kidney Function in the General Population

Sugiura¹,

Takase²,

Ohte³

et al. 2018

Kidney Blood Press Res

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“…This loss of SK channel function in the PVN of HS-fed rats potentially primes the SNS through loss of spike frequency adaptation within presympathetic PVN neurons. Our data are of considerable interest when taken into account with previous studies demonstrating augmentations in excitability of the SNS after HS treatment, including one very recent study (49) indicating that a HS diet alone contributes to exaggerated SNA and ABP responses to various excitatory stimuli. Similar to evidence that HS intake can augment the excitability of brain stem SNS circuitry, the present study shows that a HS diet alone has the ability sensitize the neural circuitry in the PVN.…”

Section: Discussionsupporting

confidence: 60%

Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus

Larson

Gui

Huber

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced small-conductance Ca(2+)-activated K(+) (SK) current and increased excitability of presympathetic neurons in the paraventricular nucleus (PVN) in ANG II-salt HTN. Here, we hypothesized that ANG II-salt HTN would be accompanied by altered PVN SK channel activity, which may contribute to sympathoexcitation in vivo. In anesthetized rats with normal salt (NS) intake, bilateral PVN microinjection of apamin (12.5 pmol/50 nl each), the SK channel blocker, remarkably elevated splanchnic sympathetic nerve activity (SSNA), renal sympathetic nerve activity (RSNA), and mean arterial pressure (MAP). In contrast, rats with ANG II-salt HTN demonstrated significantly attenuated SSNA, RSNA, and MAP (P < 0.05) responses to PVN-injected apamin compared with NS control rats. Next, we sought to examine the individual contributions of HS and subcutaneous infusion of ANG II on PVN SK channel function. SSNA, RSNA, and MAP responses to PVN-injected apamin in rats with HS alone were significantly attenuated compared with NS-fed rats. In contrast, sympathetic nerve activity responses to PVN-injected apamin in ANG II-treated rats were slightly attenuated with SSNA, demonstrating no statistical difference compared with NS-fed rats, whereas MAP responses to PVN-injected apamin were similar to NS-fed rats. Finally, Western blot analysis showed no statistical difference in SK1-SK3 expression in the PVN between NS and ANG II-salt HTN. We conclude that reduced SK channel function in the PVN is involved in the sympathoexcitation associated with ANG II-salt HTN. Dietary HS may play a dominant role in reducing SK channel function, thus contributing to sympathoexcitation in ANG II-salt HTN.

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“…Consistent with the above notion, acute or chronic intracerebroventricular (ICV) infusion of hypertonic NaCl increases ABP in rodents 7-11 . Such responses are enhanced by a high salt diet 12 or exaggerated in salt-sensitive strains such as the Dahl-salt-sensitive rat 7, 8 . Lastly, lesion or interruption of neurotransmission in various hypothalamic structures including the lamina terminalis and hypothalamic paraventricular nucleus (PVH) attenuate the increase in ABP produced by acute or chronic central infusions of hypertonic NaCl 12-14 and also antagonize the development of salt-sensitive hypertension in several experimental models 15-19 .…”

Section: Introductionmentioning

confidence: 99%

“…Such responses are enhanced by a high salt diet 12 or exaggerated in salt-sensitive strains such as the Dahl-salt-sensitive rat 7, 8 . Lastly, lesion or interruption of neurotransmission in various hypothalamic structures including the lamina terminalis and hypothalamic paraventricular nucleus (PVH) attenuate the increase in ABP produced by acute or chronic central infusions of hypertonic NaCl 12-14 and also antagonize the development of salt-sensitive hypertension in several experimental models 15-19 . These hypothalamic circuits raise SNA and ABP through a pathway that involves the epithelial sodium channel and ouabain signaling 1, 2 .…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla

et al. 2015

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Elevated NaCl concentrations of the cerebrospinal fluid (CSF) increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and receive mono- or poly-synaptic inputs from several hypothalamic structures responsive to hypernatremia. Therefore, the present study investigated the contribution of RVLM neurons to the SNA and pressor response to CSF hypernatremia. Lateral ventricle infusion of 0.15M, 0.6M, and 1.0M NaCl (5µL/10 min) produced concentration-dependent increases in lumbar SNA, adrenal SNA, and arterial blood pressure (ABP) despite no change in splanchnic SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or acute lesion of the lamina terminalis blocked or significantly attenuated these responses, respectively. RVLM microinjection of the GABAA agonist muscimol abolished the sympathoexcitatory response to ICV infusion of 1M NaCl. Furthermore, blockade of ionotropic glutamate, but not angiotensin II type 1, receptors significantly attenuated the increase in lumbar SNA, adrenal SNA, and ABP. Finally, single-unit recordings of spinally-projecting RVLM neurons revealed three distinct populations based on discharge responses to ICV infusion of 1M NaCl: Type I excited (46%, 11/24), Type II inhibited (37%, 9/24), and Type III no change (17%, 4/24). All neurons with slow conduction velocities were Type I cells. Collectively, these findings suggest that acute increases in CSF NaCl concentrations selectively activate a discrete population of RVLM neurons through glutamate receptor activation to increase SNA and ABP.

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Dietary Salt Intake Exaggerates Sympathetic Reflexes and Increases Blood Pressure Variability in Normotensive Rats

Cited by 83 publications

References 42 publications

Dietary Salt Intake is a Significant Determinant of Impaired Kidney Function in the General Population

Dietary Salt Intake is a Significant Determinant of Impaired Kidney Function in the General Population

Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus

Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla

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