A comparative study of renal function in the desert-adapted spiny mouse and the laboratory-adapted C57BL/6 mouse: response to dietary salt load

2007 ◽  
Vol 293 (4) ◽  
pp. F1093-F1098 ◽  
Author(s):  
Hayley Dickinson ◽  
Karen Moritz ◽  
E. Marelyn Wintour ◽  
David W. Walker ◽  
Michelle M. Kett
Keyword(s):  
Renal Plasma Flow ◽  
Plasma Osmolality ◽  
High Salt ◽  
Spiny Mouse ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spiny Mice ◽  
Mouse Response ◽  
The Impact

The desert-adapted spiny mouse has a significantly lower glomerular number, increased glomerular size, and a more densely packed renal papillae compared with the similar-sized laboratory-adapted C57BL/6 mouse. In the present study we examined the functional consequences of these structural differences in young adult male spiny and C57BL/6 mice and detailed the impact of 1 wk of a high-salt (10% wt/wt NaCl) diet. Basal food and water intake, urine and feces production, and urinary electrolyte concentrations were not different between species, although urinary urea concentrations were higher in spiny mice ( P < 0.05). On normal salt, MAP of the anesthetized spiny mouse was ∼18 mmHg lower, effective renal plasma flow (ERPF) was 40% lower ( P < 0.001), and glomerular filtration rate (GFR) tended to be lower than in the C57BL/6 mouse. On the high-salt diet, both species had similar 24-h NaCl excretions; but C57BL/6 mice required a significantly increased amount of water (lower urine NaCl concentration) than the spiny mice. Filtration fraction was greater in both species on the high-salt diet. Spiny mice had greater GFR and ERPF after the high-salt diet, whereas the C57BL/6 mouse showed little change in GFR. The ability of the spiny mouse to tolerate a significantly higher plasma osmolality after salt, measured by a decreased drinking response, and the ability to increase ERPF at a lower MAP are features that allow this species to conserve water more efficiently than can be done in the C57BL/6 mouse. These features are important, particularly since the desert mouse has a smaller kidney, with fewer nephrons.

scholarly journals High Salt Diet Down Regulates TREM2 Expression and Blunts Efferocytosis of Macrophage After Acute Ischemic Stroke

2020 ◽  
Author(s):  
Mengyan Hu ◽  
Yinyao Lin ◽  
Xuejiao Men ◽  
Qiang Zhu ◽  
Danli Lu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Disease Severity ◽  
High Salinity ◽  
Macrophage Polarization ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Post Stroke ◽  
The Impact

Abstract Background: High salt diet (HSD) is one of the major risk factors for acute ischemic stroke (AIS). As a potential mechanism, surplus salt intake primes macrophage towards a proinflammatory phenotype. The study investigated whether HSD could blunt efferocytosis of macrophage after ischemic stroke, which was a vital process that alleviated post stroke neuroinflammation. Besides, the underlying mechanism was explored.Methods: Wild type male C57/Bl6 mice were fed with fodder containing 8% sodium chloride for 4 weeks and subjected to transient middle cerebral occlusion (tMCAO). Disease severity, macrophage polarization as well as their efferocytic activities were evaluated. In in vitro study, bone marrow derived macrophages were cultured and the impact of high salinity environment on their efferocytic capacity, as well as their expression of phagocytic molecules were analyzed. The relationship of sodium concentration, macrophage phenotype, and disease severity in AIS patients with ischemic stroke was explored. Results: HSD-fed-mice displayed increased infarct volume and aggravated neurological deficiency. Mice fed with HSD suffered exacerbated neural inflammation as higher level of inflammatory mediators and immune cells infiltration were documented. Polarization shift towards pro-inflammatory phenotype impaired efferocytosis of infiltrated macrophages within stroke lesion in HSD-fed-mice were detected. As was uncovered by PCR array, macrophage expression of triggering receptor expressed on myeloid cells 2 (TREM2), a receptor relevant with phagocytosis, was down regulated in high salt environment. Enhancing TREM2 signaling restored the efferocytosis capacity and cellular inflammatory resolution of macrophages in high salinity environment. In AIS patients, high concentration of urine sodium was correlated with lower expression of TREM2 and detrimental stroke outcomes.Conclusions: HSD blunted efferocytic capacity of macrophages through down regulating the expression of TREM2, thus impeded inflammatory resolution after ischemic stroke. Enhancing TREM2 signaling in monocyte/macrophage could be a promising therapeutic strategy to enhance efferocytosis and promote post-stroke inflammatory resolution.

scholarly journals Excessive dietary salt promotes aortic stiffness in murine renovascular hypertension

2020 ◽  
Vol 318 (5) ◽  
pp. H1346-H1355 ◽  
Author(s):  
Leon J. DeLalio ◽  
Scott Hahn ◽  
Pedro L. Katayama ◽  
Megan M. Wenner ◽  
William B. Farquhar ◽  
...  
Keyword(s):  
Aortic Stiffness ◽  
Vascular Dysfunction ◽  
Experimental Models ◽  
High Salt ◽  
Mesenteric Arteries ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood ◽  
2K1c Hypertension

High dietary salt exaggerates hypertension in multiple experimental models. Here we demonstrate that a high-salt diet produces a greater increase in arterial blood pressure at 1 wk after induction of 2-kidney, 1-clip (2K1C) hypertension but not at 3 wk. Interestingly, 2K1C mice fed a high-salt diet displayed an exaggerated pulse pressure, elevated pulse wave velocity, and reduced endothelium-dependent vasodilation of the aorta but not mesenteric arteries. These findings suggest that dietary salt may interact with underlying cardiovascular disease to promote selective vascular dysfunction and aortic stiffness.

scholarly journals High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis

2013 ◽  
Vol 81 (6) ◽  
pp. 2258-2267 ◽  
Author(s):  
Jennifer A. Gaddy ◽  
Jana N. Radin ◽  
John T. Loh ◽  
Feng Zhang ◽  
M. Kay Washington ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Content Type ◽  
Dietary Salt Intake ◽  
Regular Diet ◽  
H Pylori

ABSTRACTPersistent colonization of the human stomach withHelicobacter pyloriis a risk factor for gastric adenocarcinoma, andH. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT)cagA+H. pyloristrain or an isogeniccagAmutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with thecagAmutant strain (P< 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with thein vitroresults, we detected increasedcagAtranscriptionin vivoin animals fed a high-salt diet compared to those on a regular diet. Animals infected with thecagAmutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects ofcagA+H. pyloristrains.

Effects of high-salt diet on CYP450-4A ω-hydroxylase expression and active tone in mesenteric resistance arteries

2005 ◽  
Vol 288 (4) ◽  
pp. H1557-H1565 ◽  
Author(s):  
Jingli Wang ◽  
Richard J. Roman ◽  
John R. Falck ◽  
Lourdes de la Cruz ◽  
Julian H. Lombard
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Resistance Arteries ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Vasoconstrictor Response ◽  
Cytochrome P 450

This study investigated the role of changes in the expression of the cytochrome P-450 4A (CYP450-4A) enzymes that produce 20-hydroxyeicosatetraenoic acid (20-HETE) in modulating the responses of rat mesenteric resistance arteries to norepinephrine (NE) and reduced Po2 after short-term (3-day) changes in dietary salt intake. The CYP450-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR in arteries obtained from rats fed a high-salt (HS, 4% NaCl) diet, whereas only the CYP450-4A3 isoform was detected in vessels from rats fed a low-salt (LS, 0.4% NaCl) diet. Expression of the 51-kDa CYP450-4A protein was significantly increased by a HS diet. Inhibiting 20-HETE synthesis with 30 μM N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE in arteries obtained from rats fed either a LS or HS diet, but NE sensitivity after DDMS treatment was significantly lower in vessels from rats on a HS diet. DDMS treatment also restored the vasodilator response to reduced Po2 that was impaired in arteries from rats on a HS diet. These findings suggest that 1) a HS diet increases the expression of CYP450-4A enzymes in the mesenteric vasculature, 2) 20-HETE contributes to the vasoconstrictor response to NE in mesenteric resistance arteries, 3) the contribution of 20-HETE to the vasoconstrictor response to NE is greater in rats fed a HS diet than in rats fed a LS diet, and 4) upregulation of the production of 20-HETE contributes to the impaired dilation of mesenteric resistance arteries in response to hypoxia in rats fed a HS diet.

Effect of Salt Intake and Potassium Supplementation on Urinary Renalase and Serum Dopamine Levels in Chinese Adults

Cardiology ◽  
2015 ◽  
Vol 130 (4) ◽  
pp. 242-248 ◽  
Author(s):  
Yang Wang ◽  
Dan Wang ◽  
Chao Chu ◽  
Jian-Jun Mu ◽  
Man Wang ◽  
...  
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
High Potassium ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Potassium Intake ◽  
Potassium Supplementation ◽  
Low Salt

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.

Salt-sensitive hypertension develops after transient induction of ANG II-dependent hypertension in Cyp1a1-Ren2 transgenic rats

2005 ◽  
Vol 288 (4) ◽  
pp. F810-F815 ◽  
Author(s):  
Laura L. Howard ◽  
Matthew E. Patterson ◽  
John J. Mullins ◽  
Kenneth D. Mitchell
Keyword(s):  
Blood Pressure ◽  
Renal Plasma Flow ◽  
Systolic Pressure ◽  
High Salt ◽  
Ang Ii ◽  
Transgenic Rats ◽  
High Salt Diet ◽  
Blood Pressure Elevation ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

Transient exposure to ANG II results in the development of salt-sensitive hypertension in rats. This study was performed to determine whether a transient hypertensive episode can induce salt-sensitive hypertension in transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name TGR(Cyp1a1-Ren2)]. Systolic blood pressures were measured in conscious male Cyp1a1-Ren2 rats ( n = 6) during control conditions and during dietary administration of indole-3-carbinol (I3C; 0.15%, wt/wt), for 14 days. Systolic pressure increased from 135 ± 5 to 233 ± 7 mmHg by day 14. I3C administration was terminated and blood pressure returned to normal levels (137 ± 5 mmHg) within 10 days. Subsequently, the rats were placed on a high-salt diet (8% NaCl) for 10 days. Systolic pressure increased by 34 ± 2 mmHg throughout 10 days of the high-salt diet. Neither glomerular filtration rate nor renal plasma flow was altered in Cyp1a1-Ren2 rats with salt-sensitive hypertension. In a separate group of male Cyp1a1-Ren2 rats ( n = 6) transiently induced with 0.15% I3C for 14 days, administration of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, 2 mM) attenuated the increase in systolic pressure induced by high salt. Systolic pressure increased by only 11 ± 1 mmHg throughout 8 days of a high-salt diet and tempol administration. Thus transient induction of ANG II-dependent hypertension via activation of the Cyp1a1-Ren2 transgene induces salt-sensitive hypertension in these transgenic rats. The attenuation by tempol of the high salt-induced blood pressure elevation indicates that ANG II-induced production of superoxide anion contributes to the development of salt-sensitive hypertension after transient induction of ANG II-dependent hypertension.

scholarly journals Transcriptome Sequencing Reveals High-Salt Diet-Induced Abnormal Liver Metabolic Pathways in Mice

2021 ◽  
Author(s):  
Yanping Li ◽  
Yufei Lyu ◽  
Jing Huang ◽  
Kun Huang ◽  
Jiufei Yu
Keyword(s):  
Liver Dysfunction ◽  
Metabolic Pathways ◽  
Transcriptome Sequencing ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Theoretical Support ◽  
Retinol Metabolism ◽  
Parenchymal Injury ◽  
The Impact

Abstract Background: Although salt plays an important role in maintaining the normal physiological metabolism of the human body, many potential abnormalities in liver, especially with normal pathological results, caused by high-salt diet are not well characterized. Methods: Eight-week-old female C57BL/6 mice were randomly divided into a normal group and a high salt group. After feeding with normal or sodium-rich chow (containing 6% NaCl) for 6 weeks. Liver injury were evaluated and the influences of a high-salt diet on liver were analyzed by transcriptome sequencing. Results: We found that although no liver parenchymal injury was found after high-salt feeding, many metabolic abnormalities had formed based on transcriptome sequencing results. GO and KEGG enrichment analyses of differentially expressed genes revealed that at least 15 enzyme activities and the metabolism of multiple substances were affected by a high-salt diet. Moreover, a variety of signaling, and metabolic pathways, as well as biological functions, including some known pathways and many novel ones, such as retinol metabolism, linoleic acid metabolism, steroid hormone biosynthesis, and signaling pathways, were involved in liver dysfunction due to a high-salt diet. Conclusions: High-salt diet could induce a serious abnormal liver metabolic pathway in mice, although substantial damage has not yet been shown. This study is the first to reveal the impact of a high-salt diet on the liver at the omics level, and provides theoretical support for potential clinical risk evaluation, pathogenic mechanisms, and drug design for combating liver dysfunction, and this study also provides a serious candidate direction for further research on the physiological impacts of high-salt diets.

Regulation ofP-450 4A activity in the glomerulus of the rat

1999 ◽  
Vol 276 (6) ◽  
pp. R1749-R1757 ◽  
Author(s):  
Osamu Ito ◽  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Salt Intake ◽  
High Salt ◽  
Dependent Manner ◽  
Hydroxyeicosatetraenoic Acid ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Low Salt

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.

Immunoglobulin and renal abnormalities in Dahl genetically hypertensive rat

1991 ◽  
Vol 261 (6) ◽  
pp. H1895-H1902 ◽  
Author(s):  
L. A. Cowen ◽  
M. R. Harold ◽  
C. M. Chen ◽  
R. E. Abbott ◽  
D. Schachter
Keyword(s):  
Arterial Hypertension ◽  
Urinary Excretion ◽  
High Salt ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Genetically Determined ◽  
Salt Sensitive Hypertension ◽  
Ig G ◽  
Renal Abnormalities

The Dahl salt-sensitive rat (DS) is a model of genetically determined arterial hypertension exacerbated by dietary salt. We report two additional abnormalities of DS rats, which are both genetically determined and enhanced by salt: 1) immunoglobulin disorders and 2) renal dysfunctions. These abnormalities precede and are not the result of the arterial hypertension. In young, prehypertensive DS rats the plasma and tissue concentrations of immunoglobulin (Ig) G, but not of IgM or IgA, are decreased compared with those of the salt-resistant strain (DR). A high-salt diet (8.0% NaCl) decreases the plasma and tissue IgG levels of DS but not of DR rats. Reduction of IgG in the DS strain results from both decreased synthesis and increased urinary excretion. Renal dysfunction in young, prehypertensive DS animals is manifested by increased excretion of high molecular weight proteins, including albumin, IgG, IgA, and IgM. The high-salt diet increases the urinary excretion of these proteins within 1-2 days, and the effect is much greater in DS compared with DR rats. The urinary excretion of IgG is selectively increased relative to immunoglobulin light chains, IgA and IgM in DS compared with DR animals. The present studies provide new markers characteristic of the DS phenotype and pose the issue of possible genetic or functional interrelationships among the salt-sensitive hypertension, immunoglobulin disorders, and renal dysfunctions.

Reactive oxygen species may contribute to reduced endothelium-dependent dilation in rats fed high salt

2000 ◽  
Vol 279 (1) ◽  
pp. H7-H14 ◽  
Author(s):  
Deborah M. Lenda ◽  
Bryan A. Sauls ◽  
Matthew A. Boegehold
Keyword(s):  
Reactive Oxygen Species ◽  
Salt Intake ◽  
Reactive Oxygen ◽  
High Salt ◽  
Oxygen Species ◽  
Dietary Salt ◽  
No Donor ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake

In normotensive rats, an increase in dietary salt leads to decreased arteriolar responsiveness to acetylcholine (ACh) because of suppressed local nitric oxide (NO) activity. We evaluated the possibility that generation of reactive oxygen species in the arteriolar wall is responsible for this loss of NO activity. Arteriolar responses to iontophoretically applied ACh were examined in the superfused spinotrapezius muscle of Sprague-Dawley rats fed a low-salt (LS; 0.45%) or high-salt diet (HS; 7%) for 4–5 wk. Responses to ACh were significantly depressed in HS rats but returned to normal in the presence of the oxidant scavengers superoxide dismutase + catalase or 2,2,6,6-tetamethylpiperidine- N-oxyl (TEMPO) + catalase. Arteriolar responses to the NO donor sodium nitroprusside were similar in HS and LS rats. Arteriolar and venular wall oxidant activity, as determined by reduction of tetranitroblue tetrazolium, was significantly greater in HS rats than in LS rats. Exposure to TEMPO + catalase reduced microvascular oxidant levels to normal in HS rats. These data suggest that a high-salt diet leads to increased generation of reactive oxygen species in striated muscle microvessels, and this increased oxidative state may be responsible for decreased endothelium-dependent responses associated with high salt intake.

Sign in / Sign up

Export Citation Format

Share Document