Speed JS, Hyndman KA, Roth K, Heimlich JB, Kasztan M, Fox BM, Johnston JG, Becker BK, Jin C, Gamble KL, Young ME, Pollock JS, Pollock DM. High dietary sodium causes dyssynchrony of the renal molecular clock in rats. Am J Physiol Renal Physiol 314: F89-F98, 2018. First published September 27, 2017; doi:10.1152/ajprenal.00028.2017.-Dyssynchrony of circadian rhythms is associated with various disorders, including cardiovascular and metabolic diseases. The cell autonomous molecular clock maintains circadian control; however, environmental factors that may cause circadian dyssynchrony either within or between organ systems are poorly understood. Our laboratory recently reported that the endothelin (ET-1) B (ET) receptor functions to facilitate Na excretion in a time of day-dependent manner. Therefore, the present study was designed to determine whether high salt (HS) intake leads to circadian dyssynchrony within the kidney and whether the renal endothelin system contributes to control of the renal molecular clock. We observed that HS feeding led to region-specific alterations in circadian clock components within the kidney. For instance, HS caused a significant 5.5-h phase delay in the peak expression of Bmal1 and suppressed Cry1 and Per2 expression in the renal inner medulla, but not the renal cortex, of control rats. The phase delay in Bmal1 expression appears to be mediated by ET-1 because this phenomenon was not observed in the ET-deficient rat. In cultured inner medullary collecting duct cells, ET-1 suppressed Bmal1 mRNA expression. Furthermore, Bmal1 knockdown in these cells reduced epithelial Na channel expression. These data reveal that HS feeding leads to intrarenal circadian dyssynchrony mediated, in part, through activation of ET receptors within the renal inner medulla.

Impairment in the ability of the skin to properly store Na nonosmotically (without water) has recently been hypothesized as contributing to salt-sensitive hypertension. Our laboratory has shown that endothelial production of endothelin-1 (ET-1) is crucial to skin Na handling. Furthermore, it is well established that loss of endothelin type B receptor (ET) receptor function impairs Na excretion by the kidney. Thus we hypothesized that rats lacking functional ET receptors (ET-def) will have a reduced capacity of the skin to store Na during chronic high-salt (HS) intake. We observed that ET-def rats exhibited salt-sensitive hypertension with an approximate doubling in the diurnal amplitude of mean arterial pressure compared with genetic control rats on a HS diet. Two weeks of HS diet significantly increased skin Na content relative to water; however, there was no significant difference between control and ET-def rats. Interestingly, HS intake led to a 19% increase in skin Na and 16% increase in water content (relative to dry wt.) during the active phase (zeitgeber time 16) versus inactive phase (zeitgeber time 4, P < 0.05) in ET-def rats. There was no significant circadian variation in total skin Na or water content of control rats fed normal or HS. These data indicate that ET receptors have little influence on the ability to store Na nonosmotically in the skin during long-term HS intake but, rather, appear to regulate diurnal rhythms in skin Na content and circadian blood pressure rhythms associated with a HS diet.

Night shift work increases risk of cardiovascular disease associated with an irregular eating schedule. Elevating this risk is the high level of salt intake observed in the typical Western diet. Renal Na+ excretion has a distinct diurnal pattern, independent of time of intake, yet the interactions between the time of intake and the amount of salt ingested are not clear. The hypothesis of the current study is that limiting food intake to the typically inactive period in addition to high salt feeding will disrupt the diurnal rhythm of renal Na+ excretion. Male Sprague Dawley rats were placed on either normal (NS, 0.49% NaCl) or high (HS, 4% NaCl) salt diets. Rats were housed in metabolic cages and allowed food ad libitum and then subject to inactive period time-restricted feeding (iTRF) for 5 days. As expected, rats fed NS and allowed food ad libitum had a diurnal pattern of Na+ excretion. The diurnal pattern of Na+ excretion was not significantly different after 5 days of iTRF compared to ad libitum rats. In response to HS, the diurnal pattern of Na+ excretion was similar to NS fed rats. However, this pattern was attenuated after 5 days of HS iTRF. The diurnal excretion pattern of urinary aldosterone was abolished in both NS iTRF and HS iTRF rats. These data support the hypothesis that high salt intake combined with iTRF impairs circadian mechanisms associated with renal Na+ excretion.

ObjectivesPrevious studies have indicated that point‐of‐care ultrasonography (POCUS) of the gastric antrum can predict the adequacy of fasting before surgery and anesthesia. The aim of this study was to evaluate the utility of gastric POCUS in patients undergoing upper gastrointestinal (GI) endoscopy procedures.MethodsWe performed a single‐center cohort study in patients undergoing upper GI endoscopy. Consenting patient's gastric antrum was scanned before anesthetic care for endoscopy to determine the cross‐sectional area (CSA) and qualitatively determine safe and unsafe contents. Further, an estimate of residual gastric volume was determined using the formula and the nomogram methods. Subsequently, gastric secretions aspirated during endoscopy were quantified and further correlated with nomogram and formula‐based assessments. No patient required a change in the primary anesthetic plan except for using rapid sequence induction in those with unsafe contents on POCUS scans.ResultsQualitative ultrasound measurements consistently determined safe and unsafe gastric residual contents in 83 patients enrolled in the study. Unsafe contents were determined by qualitative scans in 4 out of 83 cases (5%) despite adequate fasting status. Quantitatively, only a moderate correlation was demonstrated between measured gastric volumes and nomogram (r = .40, 95% CI: 0.20, 0.57; P = .0002) or formula‐based (r = .38, 95% CI: 0.17, 0.55; P = .0004) determinations of residual gastric volumes.ConclusionIn daily clinical practice, qualitative POCUS determination of residual gastric content is a feasible and useful technique to identify patients at risk of aspiration before upper GI endoscopy procedures.

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