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Fulltext Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat

Greenwood MP, Greenwood M, Paton JF, Murphy D

PLoS One, 2014;9(8):e104802.
PMID: 25111786 DOI: 10.1371/journal.pone.0104802

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.

Matched MeSH terms: Sodium Chloride, Dietary/pharmacology*
Fulltext Link Between Dietary Sodium Intake, Cognitive Function, and Dementia Risk in Middle-Aged and Older Adults: A Systematic Review

Mohan D, Yap KH, Reidpath D, Soh YC, McGrattan A, Stephan BCM, et al.

J Alzheimers Dis, 2020;76(4):1347-1373.
PMID: 32675410 DOI: 10.3233/JAD-191339

BACKGROUND: A key focus for dementia risk-reduction is the prevention of socio-demographic, lifestyle, and nutritional risk factors. High sodium intake is associated with hypertension and cardiovascular disease (both are linked to dementia), generating numerous recommendations for salt reduction to improve cardiovascular health.
OBJECTIVE: This systematic review aimed to assess, in middle- and older-aged people, the relationship between dietary sodium intake and cognitive outcomes including cognitive function, risk of cognitive decline, or dementia.
METHODS: Six databases (PubMed, EMBASE, CINAHL, Psych info, Web of Science, and Cochrane Library) were searched from inception to 1 March 2020. Data extraction included information on study design, population characteristics, sodium reduction strategy (trials) or assessment of dietary sodium intake (observational studies), measurement of cognitive function or dementia, and summary of main results. Risk-of-bias assessments were performed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tool.
RESULTS: Fifteen studies met the inclusion criteria including one clinical trial, six cohorts, and eight cross-sectional studies. Studies reported mixed associations between sodium levels and cognition. Results from the only clinical trial showed that a lower sodium intake was associated with improved cognition over six months. In analysis restricted to only high-quality studies, three out of four studies found that higher sodium intake was associated with impaired cognitive function.
CONCLUSION: There is some evidence that high salt intake is associated with poor cognition. However, findings are mixed, likely due to poor methodological quality, and heterogeneous dietary, analytical, and cognitive assessment methods and design of the studies. Reduced sodium intake may be a potential target for intervention. High quality prospective studies and clinical trials are needed.

Matched MeSH terms: Sodium Chloride, Dietary/pharmacology*
Fulltext The Association of Estrogen Receptor-β Gene Variation With Salt-Sensitive Blood Pressure

Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al.

J Clin Endocrinol Metab, 2017 11 01;102(11):4124-4135.
PMID: 28938457 DOI: 10.1210/jc.2017-00957

Context: Hypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.
Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.
Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.
Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.
Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.

Matched MeSH terms: Sodium Chloride, Dietary/pharmacology
Salt: an ineffective vehicle for iodine delivery to young children in rural Sarawak

Foo LC, Zainab T, Nafikudin M, Letchuman GR

Ann Endocrinol (Paris), 1996;57(6):470-5.
PMID: 9084692

The urinary iodine excretions of women (15-40 y) and young children (< or = 6 y) from two longhouse villages in the iodine-deficient district of Lubok Antu, Sarawak, were compared. One longhouse (Mengkak) was provided with freshly produced iodized salt every two months (one kg per family) while the other (Menjiling) was provided with iodized water via fortification of the village piped-water supply. Spot urines were collected for iodine determination at baseline and at 6 and 12 months after the start of the study. Salt and water samples were collected at monthly intervals. Goiter assessment was performed on the women at the start and end of the one-year study. The mean iodine concentrations in the salt samples from Mengkak and Menjiling were, respectively, 47.1 +/- 9.7 mg/kg (n = 60) and 0.8 +/- 3.4 mg/kg (n = 60) while the mean iodine concentration in the water samples from Menjiling was 138.6 +/- 43.2 micrograms/L (n = 24); iodine could not be detected in the water samples from Mengkak. There were significant and sustained increases in median urinary iodine excretions of both women and young children in Menjiling; in Mengkak, however, significant and sustained increases in median urinary iodine excretions were observed only in women while the median urinary iodine excretions of children remained essentially unchanged throughout the study period. Goiter prevalences in the women were reduced in both longhouses. The above observations reveal the inadequacy of iodized salt as a vehicle for iodine delivery to young rural Sarawakian children and indicate the need for other means of delivering supplemental iodine to this age group in areas where salt iodization is the only strategy for IDD control. In contrast, iodization of village water supply by itself is adequate in delivering iodine uniformly to the whole community.

Matched MeSH terms: Sodium Chloride, Dietary/pharmacology