Effect Of Dietary Salt Research Articles

The Effects of Dietary Salt on Blood Pressure Variability, Cerebral Perfusion and Cognitive Function in Young-Adult Male Rats

Background: There is controversy about the relationship between dietary salt intake and cognitive function. Experimental studies showed that extremely high salt diets increased blood pressure (BP) levels, leading to cognitive impairment. However, extremely high salt diets are not clinically relevant. The present study examined how high dietary salt could affect cognitive function and whether these effects are via BP stability and cerebral hypoperfusion. Methods: SD rats (male, young adult) were on the control diet (0.4% NaCl), low salt diet (0.1% NaCl), or high salt diets (with three does at 1%, 2%, or 4% NaCl) for 12 weeks. BP levels, heart rate (HR), and BP variability (SD and CV) were measured repeatedly at baseline, 1, 2, 3, 4, 6, 8, and 12 weeks after the onset of the diet. Anxiety and cognitive function (open field, novel object recognition, and T-maze) were measured repeatedly at baseline, 4, 8, and 12 weeks after the onset of the diet. Blood Na+ and cerebral blood flow (CBF) were measured at the endpoint. Results: Rats with the low salt diet showed significantly reduced systolic BP (SBP) and diastolic BP (DBP) levels compared to those with the control diet and high salt diets at 8 weeks after the onset of the diet. Notably, rats with the low salt diet had the highest SBP variability (SBPV) and DBPV, while those with the control diet showed the lowest SBPV and DBPV. In high salt diet groups, SBPV and DBPV increased in a dose-dependent manner. There is no significant difference in HR between groups. Rats only with a 4% NaCl diet showed worse cognitive function compared to rats with low salt and control diet 8 weeks after the onset. Blood Na+ was similar between groups. Interestingly, the high salt diet increased the CBF in a dose-dependent manner. The CBF of the low salt diet was similar to those with 2% salt die, and the CBF of the control group was the lowest. Conclusions: This study suggests that a moderate-high salt diet would not affect cognitive function in young-adult male SD rats. Only consumption of an extremely high salt diet impaired cognitive function, and this harmful effect was not via cerebral hypoperfusion. Moreover, both low and high salt diets increased BPV. This research was funded by the START-UP FUNDING OF HANGZHOU NORMAL UNIVERSITY, grant number 4255C50221204123 (Dr. Fen Sun). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Dietary Salt and Zinc Level on Growth Performance and Fecal Dry Matter of Nursery Pigs

Effect of Dietary Salt and Zinc Level on Growth Performance and Fecal Dry Matter of Nursery Pigs

P1691Impact of dose and duration of dietary salt reduction on blood pressure levels: systematic review and meta-analysis of randomised trials

Abstract Background Authoritative medical and public health agencies in most countries advise to reduce population dietary salt intake to under 5–6 g/day as a strategy for preventing high blood pressure and cardiovascular disease. However, there is still dispute about whether salt reduction should be adopted by all populations. In addition, the effect of duration of dietary salt reduction has not been sufficiently investigated. Purpose To understand the effect of dietary salt reduction on blood pressure and the impact of intervention duration. Methods A systematic review and meta-analysis was conducted. Randomized controlled trials that allocated participants to low and high salt intake, without confounding from unequal concomitant interventions, were included. We excluded studies done in individuals younger than 18 years, pregnant women, individuals with renal disease or heart failure, and studies with sodium excretion estimated from spot urine. Random effect meta-analysis was used to generate pooled estimates of the effect on 24-hour urinary sodium excretion, systolic and diastolic blood pressure. Multivariate meta-regression was used to quantify the dose response effect of dietary salt on blood pressure change and to understand the impact of the intervention duration. Results 125 studies were included with 162 data points extracted. Ninety-nine data points (61%) had interventions under 4 weeks. Overall, 24-hour urinary sodium excretion changed by −141 mmol (95% CI: −156; −126), systolic blood pressure changed by −4.4 mm Hg (95% CI: −5.2; −3.7) and diastolic blood pressure changed by −2.4 mm Hg (95% CI: −2.9; −1.9). Sodium reduction resulted in a significant decrease of systolic blood pressure in all subgroups except in participants with low baseline sodium intake (<109 mmol) (Figure 1). Each 100 mmol reduction of sodium was associated with 2.7 mm Hg (95% CI: 1.0; 4.4; p=0.002) reduction of systolic blood pressure and 1.2 mm Hg (95% CI: 0.0; 2.4; p=0.046) reduction of diastolic blood pressure after adjusting for intervention duration, age, sex, race, baseline blood pressure, baseline sodium intake and interaction between age and baseline blood pressure. For the same amount of salt reduction, a 10 mm Hg higher baseline systolic blood pressure would result in 2.5 mm Hg greater reduction of systolic blood pressure. There is not enough evidence to show the impact of intervention duration. Figure 1 Conclusions Our meta-analysis showed that sodium reduction could reduce blood pressure in all adult populations regardless of age, sex and race. The effect of salt reduction on systolic blood pressure increases with higher baseline blood pressure. Further studies, designed to investigate the impact of intervention duration, are needed to understand the significance of the duration. Acknowledgement/Funding None

The effect of dietary salt on blood pressure in individuals receiving chronic dialysis: a systematic review and meta-analysis of randomised controlled trials.

Dietary salt reduction in the general population lowers blood pressure and cardiovascular risk. Despite being widely recommended, there is limited evidence as to whether this is applicable to individuals with end-stage renal disease (ESRD) receiving dialysis. Therefore, we carried out a systematic review and meta-analysis of randomised controlled trials (RCTs) investigating dietary salt reduction in individuals receiving dialysis. Studies were identified through search strategies for CENTRAL, MEDLINE, and EMBASE. Two authors independently assessed studies for eligibility with the inclusion criteria as follows: participants aged 18 years and over; a reduction in salt intake of at least 1 g/day over one week; no concomitant interventions during the study. The primary outcome was change in systolic and diastolic blood pressure. 848 reports were screened, from which 12 studies were selected for the systematic review. Four were RCTs (91 participants) that met the study inclusion criteria: three were conducted in haemodialysis patients and one in peritoneal dialysis patients; three were crossover trials and one was a parallel study. Dietary salt reduction was associated with an 8.4 mmHg reduction in systolic blood pressure (95% CI 4.8-12.0, Ι2 = 0%), and a 4.4 mmHg reduction in diastolic blood pressure (95% CI 2.2-6.6, Ι2 = 0%). In conclusion, few studies have investigated the role of dietary salt reduction in individuals with ESRD receiving dialysis, but these results suggest the importance of this intervention for lowering blood pressure in this group.

Effect of salt diet on beat-to-beat blood pressure and heart rate dynamics in hypertensive and non-hypertensive rats

mm Hg (SD: 12). Upon repeat BP measurement, the systolic BP decreased by a mean of 11 mm Hg (95% CI: 8.3 13.7, p<0.001) with 63 (86.3%) patients experiencing a lower systolic reading. Similarly, the diastolic BP decreased by a mean of 5 mm Hg (95% CI: 3.3 7.1, p<0.001) as 54 (74.0%) patients developed a lower diastolic reading. There were 48 (65.8%) patients who experienced reduction in both systolic and diastolic BP, and whose baseline characteristics did not significantly differ from the remaining patients. Repeating the HR measurement led to reduction in the pulse reading by a mean of 6.2 beats per minute (95% CI: 4.7 7.8, p<0.001) with 61 (83.6%) patients experiencing lower HR. Conclusion: Among a high-risk population of hypertensive patients, repeating measurements during the clinic appointment leads to significantly lower BP and HR readings. Our findings suggest that the repeated BP may be more representative of hypertensive status, illustrating a component of white coat hypertension. We propose the concept of ‘‘first pass’’ white coat hypertension to refer to the difference between first and second BP readings during an individual office visit. ‘‘Second pass’’ white coat hypertension may then refer to the phenomenon of persistently high BP readings in the office but normal readings at home. Recognizing the utility of obtaining a repeat set of BP and HR measurements may have significant impact on management decisions.

Effect of Salt Diet on Beat‐to‐Beat Blood Pressure Dynamics in Hypertensive and Non‐hypertensive Rats

ObjectivesBlood pressure normally exhibits substantial short and long term variability (BPV). We assessed, in salt sensitive hypertensive (SS) and non‐hypertensive (SSBN13) Dahl rats, the impact of high (HS) versus low (LS) salt diet on beat‐to‐beat BPV indices including correlation properties (detrended fluctuation analysis scale coefficient α) and complexity (Sample Entropy; SpEn)MethodsBP data were analyzed from 9 SS [HTN] and 6 SSBN13 [No‐HTN] rats: 1) after 9 weeks of LS diet (0.4%), and 2) repeated after 2 weeks of HS diet (8%). Beat‐to‐beat systolic and diastolic BP series were derived from 2‐minute data epochs (Physionet.org). SpEn, coefficient α, standard deviation (SD) and coefficient of variation (CV, %) were comparedResultsMean systolic and diastolic BP increased on HS – particularly in SS rats (Table). SD and CV were similar across groups irrespective of diet. On LS, HTN and No‐HTN exhibited similar systolic and diastolic complexity and correlation indices. On HS, 1) HTN showed an increased α (smoother) for systolic (p=0.015) and diastolic (p=0.021) BP; 2) No‐HTN showed lower SpEn (less complex) for systolic and diastolic BP (p=0.046), while corresponding α were unchanged; and 3) HTN showed higher systolic (p=0.003) and diastolic (p=0.001) α compared to No‐HTN. Changes in α (ΔHS‐LS) were greater in HTN versus No‐HTN rats for diastolic (p=0.034) and systolic (p=0.099) BP seriesConclusionHypertensive rats are more susceptible to HS with a greater rise in mean BP and reduced complexity. Yet, the comparable mean pressures in HTN and No‐HTN rats when on LS diet coupled with similar BPV dynamics suggest a protective role of low salt diet in hypertensive ratsFunding: None Study Group SS rats (HTN) SSBN13 rats (No‐HTN) Teatment LS HS ΔHS‐LS LS HS ΔHS‐LS Systolic BP mmHg 137±2ab 195±7ab 57±5b 125±2ab 155±3ab 30±2b α 0.94±0.04a 1.15±0.04ab 0.21±0.05 0.91±0.05 0.97±0.02b 0.07±0.04 SpEn 1.43±0.06 1.26±0.06 0.16±0.10 1.51±0.09a 1.24±0.08a ‐0.28±0.09 SD 4.40±0.30 5.73±0.46 1.33±0.57 4.30±1.30 5.19±0.49 0.89±0.59 CV(%) 3.2±0.2 2.9±0.2 0.26±0.34 3.5±0.4 3.4±0.4 ‐0.07±0.48 Diastolic BP mmHg 102±3a 153±7ab 51±6b 97±1a 123±3ab 26±3b α 0.98±0.04a 1.17±0.04ab 0.18±0.06b 0.94±0.04 0.95±0.01b 0.01±0.04b SpEn 1.27±0.04 1.03±0.09 0.24±0.14 1.37±0.06a 1.21±0.02a ‐0.16±0.06 SD 4.03±0.31 4.70±0.48 0.67±0.59 3.80±0.50 4.65±0.56 0.85±0.58 CV(%) 3.97±0.25 3.13±0.29 0.85±0.41 3.89±0.47 3.82±0.47 ‐0.08±0.48 Nbeats: 626‐953; data shown as mean±std err; a = P&lt;0.05 LS vs HS (within‐group); b = P&lt;0.05 SS vs SSBN13 (between‐groups; same treatment); comparisons using the rank sum and the sign rank test as appropriate

Effects of Dietary Salt on Blood Pressure

Objective: The main objective of this study is to find out the effects of dietary salt on BP in a general adult population, and to perform a systematic review of all published and non-published available scientific literature on dietary salt in relation to BP. Methods: Online search of electronic databases, Cochran systematic reviews, PubMed central, electronic journals, citation searching and Google scholar search were used to identify studies on the association between sodium and BP. A total of 67 papers were retrieved, 10 of which met the inclusion criteria and were included in the review. The authors selected the studies, extracted the data and performed narrative analyses. Most studies showed a positive association between total dietary salt and BP. The results of randomized control trials have shown a significant effect of sodium on BP. Some evidence showed that people with elevated BP and/or elders could be more sensitive to dietary salt. Results: Four trials with normotensive individuals (n=2326) and six trials with stage 1 hypertensive (n=387) were included, with follow up from 28 days to 1095 days. Six, high quality (and therefore most informative) studies and four neutral quality trials used intensive behavioral interventions. Both systolic and diastolic BP were reduced at 1 to 39 months in those given a low salt diet as compared with a usual salt (systolic by 1.7 mm Hg to 12.6 mmHg, diastolic by 0.9 mm Hg, to -10.9 mmHg), as was urinary 24-hour sodium excretion (by 42 mmol per day, to 78 mmol per day). The reduction in sodium intake and the change in BP were not related. Conclusions: Evidence suggests a small but beneficial effect of reduced dietary salt on BP, with benefits that extend to both non-hypertensive and mild to moderate hypertensive patients. A BP lowering effect of a low sodium diet may have important public health implications, although no clear dose response association could be distinguished. Furthermore, more data are needed on dietary salt from specific sources in relation to BP, and on the salt - BP relations in population subgroups.

Effect of Dietary Salt on Regulation of TGF-β in the Kidney

Dietary sodium chloride (salt) has long been considered injurious to the kidney by promoting the development of glomerular and tubulointerstitial fibrosis. Endothelial cells throughout the vasculature and glomeruli respond to increased dietary salt intake with increased production of transforming growth factor-β (TGF-β) and nitric oxide. High-salt intake activates large-conductance, voltage- and calcium-activated potassium (BK(Ca)) channels in endothelial cells. Activation of BK(Ca) channels promotes signaling through proline-rich tyrosine kinase-2, cellular-sarcoma (c-Src), Akt (also known as protein kinase B), and mitogen-activated protein kinase pathways that lead to endothelial production of TGF-β and nitric oxide. TGF-β signaling is broadly accepted as a strong stimulator of renal fibrosis. The classic description of TGF-β signaling pathology in renal disease involves signaling through Smad proteins resulting in extracellular matrix deposition and fibrosis. Active TGF-β1 also causes fibrosis by inducing epithelial-mesenchymal transition and apoptosis. By enhancing TGF-β signaling, increased dietary salt intake leads to progressive renal failure from nephron loss and glomerular and tubulointerstitial fibrosis.

Effects of Different Dietary Salt Levels on Growth and Salinity Tolerance of Angel Fish (Pterophyllum scalare)

This study investigated the effects of dietary salt (NaCl) levels on growth performance and salinity tolerance of angel fish (Pterophyllum scalare). Five diets were supplemented with 0 (control), 7.5, 15, 22.5, and 30 g kg−1 salt, respectively. Over 56 days, weight gain and specific growth rate were similar for the fish fed diets supplemented with 0 (control), 22.5, and 30 g kg−1 salt (P > 0.05), but slightly lower than fish fed the 7.5 and 15 g kg−1 salt diets. Results showed that addition of 7.5 and 15 g kg−1 salt to diets slightly increased specific growth rate (SGR), while decreased food coefficient ratio (FCR) and the highest final weight were observed in fish fed the diet containing 7.5 g kg−1 salt. There was no significant difference in survival rate among groups at experimental period (P > 0.05). At the end of experiment, the angel fish were exposed to salinity stress (6, 9, and 12 ppt). There was no significant obvious trend in survival index after 48-h salinity stress (P < 0.05).

Celecoxib does not alter cardiovascular and renal function during dietary salt loading

1. Cyclo-oxygenase-2 (COX-2)-derived prostaglandins are important in controlling sodium excretion and renin release. In the present study, we tested the hypothesis that a clinical dose of celecoxib would impair urinary sodium excretion and elevate blood pressure (BP) during dietary salt loading. 2. Twelve normotensive individuals (mean (± SEM) age 35 ± 2 years) completed two separate 17 day dietary perturbations, one taking 200 mg/day celecoxib (CX2) and the other taking placebo (PL), randomized with a 1 month wash out. The controlled 17 day diet consisted of a 3 day run-in diet, 7 days of a low-salt (LS, 20 mmol sodium/day) diet and 7 days of a high-salt diet (HS, 350 mmol sodium/day) diet. The order in which the diets were applied was randomized. Data were collected on the last day of the LS and HS diets. 3. Plasma and urinary prostaglandins were modestly lower during celecoxib (P < 0.05). Urinary sodium excretion was greater (P < 0.01) during the HS diet (253 ± 10 vs 281 ± 27 mmol/24 h for PL vs CX2, respectively) compared with the LS diet (14 ± 3 vs 17 ± 7 mmol/24 h for PL vs CX2, respectively; P(drug) = 0.26). Celecoxib did not alter creatinine clearance (P > 0.50). Twenty-four hour mean arterial BP was similar during PL (87 ± 2 vs 87 ± 2 mmHg for LS and HS, respectively) and CX2 (88 ± 2 vs 87 ± 2 mmHg for LS and HS, respectively; P = 0.85), with no effect of dietary salt (P > 0.80). Plasma renin activity, angiotensin II and aldosterone were all suppressed with dietary salt loading (P < 0.05), with no effect of drug (P > 0.35). 4. In conclusion, blood pressure and renal function were not adversely affected by celecoxib, even during dietary salt loading. These findings support current guidelines suggesting minimal cardiovascular risks associated with short-term, low-dose use of celecoxib in young to middle-aged adults.

Simple advice to reduce salt intake

The effect of dietary salt on health has caused much debate and a seemingly ongoing battle between the medical fraternity and the food industry.1 In the UK, more than the US, this appears to be being won by the medical establishment with a greater public awareness of salt consumption through government campaigns and improved food labelling.2 As yet, it is not clear whether these added measures have had a net effect in actually reducing sodium intake and although food products are being labelled more clearly, many continue to contain large amounts of added salt. The scientific data meriting reduced sodium intake also continues to mount. A Cochrane review states that in hypertensive patients a modest reduction in dietary salt intake over 4 or more weeks led, on average, to a decrease of 4.7 mmHg systolic blood pressure and 2.7 mmHg diastolic blood pressure, although it was unclear in this study whether the same reduction in salt intake lead to a decrease in cardiovascular risk or mortality.3 A subsequent study by The Trials of Hypertension Prevention Collaborative Research Group confirmed that reduced sodium intake lowers blood pressure in addition to the possible reduction of long-term cardiovascular events.4 With increasing evidence to recommend a reduced sodium intake the Food Standards Agency recommends that we should all aim to consume no more than 6 g of salt (2.5 g sodium) a day.2 This figure represents a compromise between the average daily UK consumption of (9–12 g) and what we actually need (1–2 g). With the mounting scientific data and government backing it is quite understandable that clinicians want clearer guidance as to how to translate methodology from successful trials into advice to a patient sitting in front of them in a consultation.5 Several of the published trials concluding that dietary salt reduction leads to a decrease in blood pressure do not give details of the advice that patients were given to reduce their overall salt intake. Other trials had tightly controlled diets where all meals in control and low-salt groups were provided for. Being able to extrapolate the results of these trials to public awareness and practice would be useful, providing the advice is both easy to understand and to follow. The first step must therefore be to put the reason for the intervention into context. Thus emphasising that even a modest (2 g) reduction of salt intake, over a relatively short period, can lead to a reduction in blood pressure, which could lead to a decreased incidence of stroke in the long term. We suggest that further advice can be delivered using a quick and easy acronym: S.A.L.T. (Box 1). Box 1 S.A.L.T. Stay away from processed foods Avoid adding salt to foods Look at sodium levels Try to eat a balanced diet

Dietary salt does not influence the disposition of verapamil enantiomers in relation to efflux transporter ABCB1 genetic polymorphism in healthy Korean subjects

To evaluate the effects of dietary salt on the stereoselective disposition of verapamil enantiomers in relation to the transporter ABCB1 2677GG/3435CC and 2677TT/3435TT haplotypes, ten healthy subjects were asked to take diets of three different salt levels for 7 days in a randomized, three-way crossover manner.The plasma concentrations of verapamil and norverapamil enantiomers were determined after a single oral dose of 240 mg verapamil on the last day of each phase. Pharmacokinetic parameters were calculated by non-compartmental analysis techniques and compared among the three different dietary salt phases.Compared with the medium salt diet, the high and low salt diets had no significant effect on the disposition of verapamil enantiomers. Moreover, the ABCB1 haplotypes did not alter the impact of dietary salt, although ABCB1 2677TT/3435TT subjects had slightly, but not significantly, higher Cmax and area under the curve (AUC) and lower Tmax for the verapamil enantiomers than did 2677GG/3435CC subjects in each salt phase.

Effects of dietary salt on the expression of drug transporters, cytochrome P4503a, and nuclear receptors in rats

Quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analyses were carried out to investigate the regulation of genes responsible for the transport and metabolism of drugs in response to different levels of salt intake. A high-salt diet compared with medium- and low-salt diets reduced the expression levels of the mdr1a and mdr1b genes in the liver and kidney, but increased their expression levels in the duodenum, jejunum, and ileum. Likewise, the expression levels of other transporters and CYP3a3 genes varied in different tissues. The expression levels of nuclear receptors, such as Pxr, Fxr, and Car, were also modulated differently in the liver, kidney, and intestines. The protein levels of Mdr1, Oct1, CYP3a, Pxr, Fxr, and Car were correlated with the changes in mRNA levels of the respective genes. In conclusion, the changes in the expression of drug transporters, metabolic enzymes, and nuclear receptors were tissue specific.

Effects of Dietary Salt on Intrarenal Angiotensin System, NAD(P)H Oxidase, COX-2, MCP-1 and PAI-1 Expressions and NF-κB Activity in Salt-Sensitive and -Resistant Rat Kidneys

Background: Chronic consumption of a high-salt diet causes hypertension (HTN) and renal injury in Dahl salt-sensitive (SSR) but not salt-resistant rats (SRR). These events are, in part, mediated by oxidative stress and inflammation in the kidney and vascular tissues. Activation of the angiotensin II type 1 (AT₁) receptor plays an important role in the pathogenesis of oxidative stress and inflammation in many hypertensive disorders. However, the systemic renin-angiotensin system (RAS) is typically suppressed in salt-sensitive HTN. This study was designed to test the hypothesis that differential response to a high-salt diet in SSR versus SRR may be related to upregulation of tissue RAS and pathways involved in inflammation and reactive oxygen species (ROS) production. Methods and Results: SSR and SRR were studied 3 weeks after consumption of high- (8%) or low-salt (0.07%) diets. The SSR consuming a low-salt diet exhibited significant increases in AT₁ receptor, cyclooxygenase (COX) 2, plasminogen activator inhibitor (PAI) and phospho-IĸB in the kidney as compared to those found in SRR. The high-salt diet resulted in severe HTN and proteinuria (in SSR but not SRR) and marked elevations of renal tissue monocyte chemoattractant protein 1, p22^phox, NADPH oxidase subunit 4, angiotensin-II-positive cell count, infiltrating T cells and macrophages and further increases in AT₁ receptor, COX-2, PAI-1 and phospho-IĸB in the SSR group. The high-salt diet significantly lowered plasma renin activity (PRA) in SRR but not in the SSR. COX-1 abundance was similar on the low-salt diet and rose equally with the high-salt diet in both groups. Among subgroups of animals fed the low-salt diet, kidney glutathione peroxidase (GPX) abundance was significantly lower in the SSR than SRR. The high-salt diet raised GPX and mitochondrial superoxide dismutase (SOD) abundance in the SRR kidneys but failed to do so in SSR. Cu/Zn-SOD abundance was similar in the subgroups of SSR and SRR fed the low-salt diet. The high-salt diet resulted in downregulation of Cu/Zn-SOD in SSR but not SRR. Conclusions: Salt sensitivity in the SSR is associated with upregulations of the intrarenal angiotensin system, ROS-generating and proinflammatory/profibrotic proteins and an inability to raise antioxidant enzymes and maximally suppress PRA in response to high salt intake. These events can contribute to renal injury with high salt intake in SSR.

Dietary salt reduces hydrogen peroxide‐dependent dilation in contracting muscle

Skeletal muscle fibers can release H2O2 during contraction. We assessed the contribution of H2O2 to the arteriolar dilation during muscle contraction, the effect of dietary salt on the magnitude of this contribution, and the mechanism(s) by which H2O2 relaxes vascular smooth muscle. Arterioles were studied in the spinotrapezius muscle of rats fed a normal or high salt (0.45%, NS; 7%, HS). Resting diameters were identical in both groups, but dilation during 2 Hz and 4 Hz contraction was significantly less in HS rats than in NS rats. Exogenous catalase, at a concentration that effectively scavenges extracellular H2O2, did not affect resting diameters in either group, but reduced the dilation during 2 Hz and 4 HZ contraction by 55±11% and 60±10%, respectively, in NS rats. In HS rats, catalase reduced dilation during 2 Hz contraction by 36±12%, and had no effect on dilation during 4 Hz contraction. Dilation in response to exogenous H2O2 was significantly greater in HS rats than NS rats, but these responses were similarly reduced in both groups by inhibition of endogenous catalase with 3-AT, or inhibition of guanylyl cyclase with ODQ. We conclude that arteriolar dilation in contracting skeletal muscle is due in part to locally produced H2O2, and that the effect of H2O2 on arteriolar tone depends in part on its metabolism by intracellular catalase and activation of guanylyl cyclase. Increased dietary salt reduces the contribution of H2O2 to this dilation, but may not change the mechanism through which it relaxes vascular smooth muscle. (NIH HL44012).

Angiotensin II compartmentalization within the kidney: effects of salt diet and blood pressure alterations

All components of the renin-angiotensin-aldosterone system are present within the kidney. Renin, renin receptor, angiotensinogen and angiotensin AT1 and AT2 receptor and aldosterone synthase messenger RNA and protein are present in close proximity to the renal vasculature and tubules. The interaction between the different components of the renin-angiotensin-aldosterone system determines the level of activity of this system and in turn may influence the regulation of blood pressure and renal sodium handling. Angiotensin through the stimulation of its subtype AT2 receptor regulates sodium excretion, renin synthesis and secretion. Aldosterone synthase mRNA and protein are expressed in glomeruli, renal vasculature and tubules, and are regulated by angiotensin AT1 receptor, diabetes and salt. Although aldosterone is known to influence renal tubular channels with the subsequent enhancement of sodium reabsorption, it is not clear if the renally produced aldosterone also influences renal sodium handling or blood pressure regulation. In addition, angiotensin II influences kidney function and structure through the stimulation of renal inflammation. New data suggest that the renal AT1 receptor plays an important role in the determination of blood pressure levels, and this effect is unique and non-redundant in the actions of extrarenal AT1 receptors. The finding of new functions and components of the renin-angiotensin-aldosterone system clearly adds new knowledge to our understanding of how angiotensin II influences the kidney and blood pressure.

The effect of dietary salt on verapamil disposition in relation to MDR1 C3435T / G2677T genotype

Although the effect of MDR1 genotype on oral bioavailability of verapamil are remained controversial, dietary salt might affect on its disposition in relation to MDR1 genetic polymorphism. To evaluate the influences of dietary salt on the enantioselective disposition of verapamil in relation to MDR1 genotype, ten healthy male subjects(5 with 3435CC/2677GG and others with 3435TT/2677TT) were enrolled in randomized crossover study. Five were served low salt diet (~1.5g/day) and others did high salt diet (25g/day) for 7 days. After a week-washout, the salt diet sequence was switched. On day 7, 14, and 21, blood and urine samples were serially collected upto 24 hours after oral dosing of 240mg verapamil. The concentration of verapamil enantiomers and its metabolites were determined using LC/MS/MS. The plasma concentrations of both enantiomers and R/S AUCinf ratios were not significantly different between trials of each diet in both genotype group. Cmax, AUC0–4hr, and AUCo-∞ of verapamil in subjects with 3435TT/2677TT were higher than in those with 3435CC/2677GG in both trial, but the difference was not statistically significant. The R/S AUCinf ratio was not also significantly different between MDR1 genotype groups. These results did not demonstrate that the dietary salt affects on the disposition of verapamil. However, this study indicated that subject with MDR1 3435T/2677T variant might show the higher oral bioavailability of verapamil than those with MDR1 3435C/2677G due to low P-glycoprotein activity. Clinical Pharmacology & Therapeutics (2005) 77, P87–P87; doi: 10.1016/j.clpt.2004.12.226

Effect of dietary salt (NaCl) level on the growth performance of liquid fed growing-finishing pigs.

Salt (NaCl) is an essential mineral and its rate of inclusion in diets has been implicated in the development and expression of biting behaviour. Falkowskiet al., (1998) found that withholding salt from diets reduced the feed intake and feed conversion ratio of weaned pigs and significantly decreased growth rate. Studies reported by Fraser (1987), suggested that heightened appetite for salt could make pigs particularly attracted to pen mates with injured tails. More recently Tsourgiannis,et al., (2002) reported that 1.5% salt inclusion levels can significantly reduce the incidence of tail-biting, providing that there is unrestricted access to fresh water. This study investigated the effect on growth performance of pigs fed liquid diets containing high and low dietary salt levels for growing/finishing pigs.

Effects of dietary salt on orthostatic tolerance, blood pressure and baroreceptor sensitivity in patients with syncope.

This study had three main objectives: to examine in patients presenting with unexplained syncope the relationship between orthostatic tolerance and dietary salt intake; to examine in patients with relative low baseline salt excretion the effect of salt loading on both orthostatic tolerance and blood pressure; and to examine the relationship between dietary salt intake and the sensitivity of the baroreceptor reflex. In 178 patients with unexplained syncope we determined 24-hour urinary sodium excretion, supine arterial blood pressure, carotid cardiac baroreceptor sensitivity (neck suction) and tolerance to orthostatic stress (head-up tilt and lower body suction). Those with low salt excretions and poor orthostatic tolerance were given salt supplements and reassessed after three months. Baseline studies revealed that patients with sodium excretions < 170 mmol/day had significantly lower orthostatic tolerance than those with higher excretions. Salt loading caused a small but significant increase in mean pressure and significant increases in orthostatic tolerance and baroreceptor sensitivity. Improved orthostatic tolerance was seen in 68 of 98 (69 %) patients in whom salt was given. These patients had significantly greater changes in baroreceptor sensitivity than those failing to improve. These results confirm the benefits of salt loading patients with posturally-related syncope. Incidence of hypertension following salt in these patients is relatively uncommon but it is advisable to monitor the effects on blood pressure.

Abnormal platelet function and calcium handling in Dahl salt-hypertensive rats.

The effect of dietary salt on platelet function and Ca(2+) homeostasis was studied in Dahl (DS) rats, a genetic model of salt-sensitive hypertension. DS rats were fed a high-salt (DSHS) or a low-salt diet (DSLS) for up to 4 weeks, and the effects of salt loading on systolic blood pressure, platelet P-selectin expression, and platelet Ca(2+) homeostasis were measured. The high-salt diet increased blood pressure and markedly increased the amount of ionomycin (IM)-releasable Ca(2+) in platelet intracellular stores (Ca(2+)/IM). The alteration in Ca(2+) stores was not prevented when the hypertension was prevented by treatment with hydralazine and reserpine. The Ca(2+) store filling during platelet exposure to 1 mmol/L Ca(2+) for 5 minutes and the rate of sarcoplasmic/endoplasmic Ca(2+) ATPase-dependent Ca(45) uptake were higher in DSHS compared with that in DSLS. There was a decrease in thrombin-induced Ca(2+) influx in platelets from DSHS; consistent with this, agonist-induced P-selectin expression was decreased. In DSLS, nitric oxide accelerated reloading of platelet Ca(2+) stores after their emptying by thrombin but failed to do so in DSHS. These results indicate that in DS rats, a high-salt diet increases sarcoplasmic/endoplasmic Ca(2+) ATPase activity and the Ca(2+)/IM but decreases the reuptake of Ca(2+) caused by nitric oxide. Decreases in Ca(2+) influx and platelet P-selectin expression might be explained by changes in intracellular Ca(2+) stores in DSHS rats, which apparently is a heritable response to a high-salt diet.