Salt intake and insulin sensitivity in healthy human volunteers

2007 ◽  
Vol 113 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Raymond R. Townsend ◽  
Shiv Kapoor ◽  
Christopher B. McFadden

The literature on salt intake and insulin sensitivity presents a mixed picture, as some studies have shown an increase, whereas others have shown a decrease, in insulin action as sodium intake is enhanced. In some cases, this may relate to the study of salt intake in patients with co-morbidities such as hypertension or diabetes. In the present study, we selected healthy normotensive lean volunteers who underwent a euglycaemic clamp following 6 days of a low-salt diet (20 mmol sodium daily) and, subsequently, 6 days of a high-salt diet (200 mmol sodium daily). Our results show an increase in insulin-mediated glucose disposal during euglycaemic clamp conditions that was significantly higher following the high-salt diet compared with the low-salt diet (7.41±0.41 compared with 6.11±0.40 mg·kg−1 of body weight·min−1 respectively; P=0.03). We measured calf blood flow before and during insulin infusion (no significant change after the two dietary salt interventions was detected) and plasma non-esterified fatty acids (also no significant differences were detected). We observed the expected increases in renin concentration and aldosterone activity in subjects on the low-salt diet, and also observed a significantly less increase in plasma noradrenaline concentration during euglycaemic insulin infusion following the high-salt compared with the low-salt diet. We propose that the 4–5-fold increase in serum aldosterone and the greater increase in plasma noradrenaline concentration following the low-salt intervention compared with the high-salt period may have contributed to the differences in insulin sensitivity following the adjustment in dietary sodium intake.

2012 ◽  
Vol 13 (3) ◽  
pp. 353-359 ◽  
Author(s):  
MA Bayorh ◽  
A Rollins-Hairston ◽  
J Adiyiah ◽  
D Lyn ◽  
D Eatman

Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E2 (PGE2). Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.2 mg pellet) in the presence of EPL (100 mg/kg/day) or APC (1.5 mM). Indirect blood pressure, prostaglandins and ALDO levels and histological changes were measured. Results: Cyclooxygenase-2 (COX-2) levels were upregulated in the renal tubules and peritubular vessels after high-salt intake, and APC attenuated renal tubular COX-2 protein expression induced by ALDO. Plasma PGE2 levels were significantly reduced by ALDO in the rats fed a low-salt diet when compared to rats fed a high-salt diet. PGE2 was blocked by EPL but increased in the presence of APC. Conclusions: The beneficial effects of EPL may be associated with an inhibition of PGE2. The mechanism underlying the protective effects of EPL is clearly distinct from that of APC and suggests that these agents can have differential roles in cardiovascular disease.


Cardiology ◽  
2015 ◽  
Vol 130 (4) ◽  
pp. 242-248 ◽  
Author(s):  
Yang Wang ◽  
Dan Wang ◽  
Chao Chu ◽  
Jian-Jun Mu ◽  
Man Wang ◽  
...  

Objective: The aim of our study was to assess the effects of altered salt and potassium intake on urinary renalase and serum dopamine levels in humans. Methods: Forty-two subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for an additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). Results: Urinary renalase excretions were significantly higher during the high-salt diet intervention than during the low-salt diet. During high-potassium intake, urinary renalase excretions were not significantly different from the high-salt diet, whereas they were significantly higher than the low-salt levels. Serum dopamine levels exhibited similar trends across the interventions. Additionally, a significant positive relationship was observed between the urine renalase and serum dopamine among the different dietary interventions. Also, 24-hour urinary sodium excretion positively correlated with urine renalase and serum dopamine in the whole population. Conclusions: The present study indicates that dietary salt intake and potassium supplementation increase urinary renalase and serum dopamine levels in Chinese subjects.


1999 ◽  
Vol 276 (6) ◽  
pp. R1749-R1757 ◽  
Author(s):  
Osamu Ito ◽  
Richard J. Roman

We recently reported that an enzyme of the cytochrome P-450 4A family is expressed in the glomerulus, but there is no evidence that 20-hydroxyeicosatetraenoic acid (20-HETE) can be produced by this tissue. The purpose of present study was to determine whether glomeruli isolated from the kidney of rats can produce 20-HETE and whether the production of this metabolite is regulated by nitric oxide (NO) and dietary salt intake. Isolated glomeruli produced 20-HETE, dihydroxyeicosatrienoic acids, and 12-hydroxyeicosatetraenoic acid (4.13 ± 0.38, 4.20 ± 0.38, and 2.10 ± 0.20 pmol ⋅ min−1⋅ mg protein−1, respectively) when incubated with arachidonic acid (10 μM). The formation of 20-HETE was dependent on the availability of NADPH and the[Formula: see text] of the incubation medium. The formation of 20-HETE was inhibited by NO donors in a concentration-dependent manner. The production of 20-HETE was greater in glomeruli isolated from the kidneys of rats fed a low-salt diet than in kidneys of rats fed a high-salt diet (5.67 ± 0.32 vs. 2.83 ± 0.32 pmol ⋅ min−1⋅ mg protein−1). Immunoblot experiments indicated that the expression of P-450 4A protein in glomeruli from the kidneys of rats fed a low-salt diet was sixfold higher than in kidneys of rats fed a high-salt diet. These results indicate that arachidonic acid is primarily metabolized to 20-HETE and dihydroxyeicosatrienoic acids in glomeruli and that glomerular P-450 activity is modulated by NO and dietary salt intake.


1996 ◽  
Vol 271 (1) ◽  
pp. R109-R114 ◽  
Author(s):  
S. W. John ◽  
A. T. Veress ◽  
U. Honrath ◽  
C. K. Chong ◽  
L. Peng ◽  
...  

Atrial natriuretic peptide (ANP)-gene knockout mice of three genotypes (+/+, +/-, and -/-) were maintained on a low-salt diet (0.008% NaCl). They were then fed either the same low-salt diet or a high-salt diet (8% NaCl) for 1 wk. No differences were found among genotypes in daily food and water intakes or in urinary volume and electrolyte excretions. Arterial blood pressures measured in anesthetized animals at the end of the dietary regimen were significantly and similarly increased in -/- compared with +/+ mice on each diet. Renal excretion of fluid and electrolytes was measured in anesthetized mice before and after acute blood volume expansion. No genotype differences were observed before volume expansion. After volume expansion the wild-type (+/+) mice had much greater saluretic responses than either the heterozygous (+/-) or the homozygous mutant (-/-) animals on the low-salt diet but not on the high-salt diet. We conclude that ANP lowers blood pressure in the absence of detected changes in renal function; ANP is not essential for normal salt balance, even on high-salt intake; and ANP is essential for the natriuretic response to acute blood volume expansion on a low-salt but not high-salt intake.


1990 ◽  
Vol 258 (6) ◽  
pp. F1579-F1583
Author(s):  
A. Dal Canton ◽  
G. Romano ◽  
G. Conte ◽  
L. De Nicola ◽  
A. Caglioti ◽  
...  

This study was performed to define the extent to which atrial natriuretic factor (ANF) contributes to upregulate salt excretion in subjects eating a high-salt diet. Eight normal volunteers were first studied at low-salt diet (80 mmol NaCl/day); urinary sodium excretion (UNaV) and plasma ANF (PANF) were measured in the basal condition and during stepwise infusion of human alpha-ANF at 2, 4, 8, and 16 ng.min-1.kg-1. Then the same subjects were shifted to a high-salt diet (400 mmol/day), and UNaV and PANF were measured in the new balance condition. At low-salt diet, UNaV averaged 0.069 meq/min, and PANF averaged 21 pg/ml; infusion of human alpha-ANF raised stepwise both UNaV and PANF (means in meq/min and pg/ml, respectively, were 0.177 and 46, 0.218 and 76, 0.360 and 86, and 0.601 and 182). Infusion of ANF caused a progressive fall of plasma aldosterone and plasma renin activity. Mean UNaV and PANF at high-salt diet were 0.301 meq/min and 35 pg/ml. Thus, by increasing experimentally PANF in a low-salt diet condition to the levels occurring physiologically in a high-salt diet condition, a significant rise in UNaV is evoked, which accounts for approximately 50% of the rise of UNaV that is necessary to balance the increased salt intake.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Ranna Chou ◽  
Anna Hara ◽  
DongDong Du ◽  
Namiko Shimizu ◽  
Hiroe Sakuyama ◽  
...  

We investigated the influence of maternal salt restriction during mating or gestation on birth rate and offspring growth in Dahl salt-sensitive rats (DS). DS were divided into 5 groups: DS fed a low-salt (0.3% NaCl, w/w) (DS-low) or high-salt (4% NaCl, w/w) diet (DS-high) during mating and DS-high or DS-low during gestation, and DS fed regular chow (0.75% NaCl, w/w) (DS-regular) throughout mating and gestation. During the unspecified periods, the rats were given regular chow. DS-low during mating delivered fewer infants than high-salt mothers (P<0.05). The birth rate on regular chow was 87%. Six out of 11 DS-low rats during pregnancy produced pups while the rats fed a high-salt diet all delivered pups (P<0.025). The pup survival rate was 67% for high-salt mothers during mating and 54% for mothers on a low-salt diet. The pup survival rate was 95% for mothers on a high-salt diet during pregnancy and 64% for mothers on a low-salt diet (P<0.0001). Seven out of 8 DS-regular rats during mating delivered 59 neonates. However, 66% of the neonates survived. A low-salt diet during mating or pregnancy lowers birth rate and the neonates from low-salt mothers during pregnancy were more likely to die than those from high-salt mothers.


1995 ◽  
Vol 89 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Gabriele Kaczmarczyk ◽  
Willehad Boemke ◽  
Dawod Zahrei-Fard ◽  
Hermann Braun

1. We studied post-prandial changes in renal function in dogs adapted to either low or high sodium intake with and without concomitant post-prandial infusion of angiotensin II. Six trained dogs were exposed to diets containing either 0.5 or 14.5 mmol Na+ day−1 kg−1 body weight (low or high sodium respectively). They were studied from 20 min before to 4 h after food intake. In half of the experiments a physiological dose of angiotensin II (4 ng min−1 kg−1 body weight) was administered after food intake for four post-prandial hours. The water intake was high and equal on both diets (91 ml day−1 kg−1 body weight). 2. On a high-salt diet post-prandial sodium excretion and urine volume increased considerably above fasting values. This post-prandial increase was attenuated when angiotensin II was infused (post-prandial sodium excretion was 31% ± 3% of intake without versus 10% ± 1% with angiotensin II, post-prandial urine volume was 22% ± 2% without versus 8% ± 1% with angiotensin II, P < 0.05). Post-prandial increases in glomerular filtration rate and fractional sodium excretion were attenuated during angiotensin II infusion in dogs on a high-salt diet. 3. On a low-salt diet post-prandial sodium excretion remained low with or without angiotensin II infusion, whereas urine volume increased post-prandially, and this increase was greater when angiotensin II was administered (40% ± 3% versus 34% ± 2% of intake, P < 0.05). 4. Angiotensin II infusion increased mean arterial pressure by an average of 12 mmHg in dogs on a high-salt diet (P < 0.05) and by 7 mmHg in dogs on a low-salt diet. In dogs on a high-salt diet, right atrial pressure was on an average 3 cmH2O higher with than without angiotensin II (P < 0.05). In animals on a low salt intake post-prandial right atrial pressure decreased slightly, but remained in the range of fasting values, during angiotensin II infusion. 5. Neither plasma osmolality nor plasma sodium concentration changed in any of the four protocols. 6. We conclude that the post-prandial effects of angiotensin II in dogs on a high water intake depend on the amount of concomitant sodium intake. Angiotensin II reduces the post-prandial diuresis and natriuresis when given to sodium-loaded dogs, whereas angiotensin II does not reduce post-prandial urine flow and sodium excretion rates in dogs on a low sodium intake and may even augment water excretion in this condition.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Peng Xu ◽  
John J Gildea ◽  
Mahabuba Akhter ◽  
Robert M Carey ◽  
Wei Yue ◽  
...  

Salt sensitivity affects approximately 20% of adults worldwide and has similar mortality and morbidity sequalae as hypertension. Research has focused on the harmful effects of a high salt diet but have not focused on the harmful effects of a low salt diet. Inverse salt sensitive (ISS) individuals require high salt intake in order to maintain a normal blood pressure. Aldosterone increases ENaC and sodium reabsorption via the mineralocorticoid receptor (MR). We previously reported that αENaC was significantly lower in ISS renal tubule cells isolated from urine (uRTC), while these cells showed higher ENaC like activities under trypsin stimulation. We hypothesized that aldosterone may act as a stimulus and play a role in ISS high blood pressure on a low salt diet (LSD). Plasma aldosterone was significantly increased on LSD in all salt study participants, and ISS individuals showed the highest aldosterone level (ISS HS 3.8±0.38, n=26; ISS LS 35±3.38, n=22; SR HS 4.34±0.18, n=180; SR LS 32.62±1.6, n=152; SS HS 4.65±0.35, n=43; SS LS 26.08±2.18, n=38; HS Vs LS, p<0.001, two-way ANOVA). Moreover, both aldosterone and plasma renin activity (PRA) were significantly lower in salt sensitive (SS) individuals on LSD (PRA LS: ISS 6.05±0.87, n=17; SR 5.94±0.36, n=108; SS 4.43±0.57, n=34; p<0.05, one-way ANOVA), indicating LSD was protective to SS individuals. Treatment of uRTCs with 1 μM aldosterone increased MR and αENaC expression in ISS but not in SR (salt resistant) cells (MR: SR VEH 12164±213; SR Aldosterone 12327±128; ISS VEH 12128±40 vs ISS Aldosterone 13506±128, n=3, p<0.001, two-way ANOVA; αENaC: SR VEH 5023±46; SR Aldosterone 4895±55; ISS VEH 4270±21 vs ISS Aldosterone 5013±113, n=3, p<0.001, two-way ANOVA). High salt treatment further decreased MR in ISS but not in SR cells (ISS: 142mM 11066±188 vs 192mM 10425±74; p<0.05, n=3 two-way ANOVA). These results are consistent with the hypothesis that ISS individuals retain excess Na + and exhibit decreased BP when compared to SR or SS individuals under high salt diet, but reabsorb more sodium and exhibit elevated blood pressure under low salt diet. Higher circulating aldosterone and ex-vivo urine derived renal cell aldosterone sensitivity under low salt conditions may be a novel diagnostic test to identify ISS individuals.


1996 ◽  
Vol 270 (6) ◽  
pp. F1027-F1037 ◽  
Author(s):  
I. Singh ◽  
M. Grams ◽  
W. H. Wang ◽  
T. Yang ◽  
P. Killen ◽  
...  

Experiments were performed to examine the effect of changes in dietary salt intake on the neuronal form of the constitutive nitric oxide synthase (ncNOS, type I NOS), renin, and angiotensinogen mRNA expression in the kidney. Three groups of Sprague-Dawley rats were studied as follows: rats maintained on a 3% Na diet plus 0.45% NaCl in the drinking fluid for 7 days (high salt), rats given a single injection of furosemide (2 mg/kg i.p.) and a 0.03% Na diet for 7 days (low salt), and rats on a diet containing 0.2% Na (control). mRNA expression was assessed with reverse transcription-polymerase chain reaction (RT-PCR) methods using cDNA prepared from samples of renal cortex and microdissected tubular segments. ncNOS PCR products were quantified by comparison with a dilution series of a mutant deletion template. Compared with their respective control, ncNOS mRNA levels in renal cortical tissue were elevated in rats on a low-salt diet and reduced in rats on a high-salt diet. Similar changes were seen in the expression of renin and angiotensinogen mRNA. Dietary salt intake did not alter the mRNA levels for ncNOS from the inner medulla or for endothelial constitutive NOS (ecNOS, type III NOS) and inducible NOS (iNOS, type II NOS) in the renal cortex. ncNOS mRNA was found in glomeruli dissected with the macula densa-containing segment (MDCS), but only at marginal levels in glomeruli without MDCS. Furthermore, a low-salt diet stimulated ncNOS mRNA in glomeruli with MDCS by 6.2-fold compared with a high-salt diet. There was no effect of salt diet on ncNOS mRNA in glomeruli without MDCS or in inner medullary collecting ducts. These results suggest that ncNOS expression in macula densa cells is inversely regulated by salt intake, thus following the known response of the renin-angiotensin system to changes in salt balance.


2002 ◽  
Vol 282 (2) ◽  
pp. H395-H402 ◽  
Author(s):  
Deborah M. Lenda ◽  
Matthew A. Boegehold

Increased salt intake attenuates the endothelium-dependent dilation of skeletal muscle arterioles by abolishing local nitric oxide (NO) activity. There is evidence of oxidative stress in arteriolar and venular walls of rats fed a high-salt diet, and depressed arteriolar responses to acetylcholine (ACh) in these rats are reversed by scavengers of reactive oxygen species (ROS). In this study, we tested the hypothesis that this salt-dependent increase in microvascular ROS and the resulting attenuation of endothelium-dependent dilation are due to increased expression and/or activity of oxidant enzymes in the microvascular wall. Resting arteriolar and venular wall oxidant activity, as assessed by tetranitroblue tetrazolium reduction, was consistently higher in the spinotrapezius muscle of rats fed a high-salt diet (7% NaCl, HS) for 4–5 wk than in those fed a normal diet (0.45% NaCl, NS) for the same duration. Western analysis of protein from isolated microvessels showed no difference between HS and NS rats in the expression of NAD(P)H oxidase or xanthine oxidase. Inhibition of NAD(P)H oxidase and/or xanthine oxidase with diphenyleneiodonium chloride and oxypurinol, respectively, reduced resting arteriolar wall oxidant activity to normal levels in HS rats but had no effect in NS rats, suggesting that the basal activities of NAD(P)H oxidase and xanthine oxidase are increased in HS microvessels. However, inhibition of these enzymes in HS rats did not restore normal arteriolar responses to ACh, suggesting that this stimulus activates an alternate source of ROS that eliminates the role of NO in the subsequent dilation.


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