scholarly journals High-salt intake enhances superoxide activity in eNOS knockout mice leading to the development of salt sensitivity

2010 ◽  
Vol 299 (3) ◽  
pp. F656-F663 ◽  
Author(s):  
Libor Kopkan ◽  
Arthur Hess ◽  
Zuzana Husková ◽  
Luděk Červenka ◽  
L. Gabriel Navar ◽  
...  
Keyword(s):  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
No Production ◽  
Wild Type ◽  
Total N ◽  
High Salt Intake ◽  
Excretion Rates ◽  
Salt Sensitive Hypertension

A deficiency in nitric oxide (NO) generation leads to salt-sensitive hypertension, but the role of increased superoxide (O2−) in such salt sensitivity has not been delineated. We examined the hypothesis that an enhancement in O2− activity induced by high-salt (HS) intake under deficient NO production contributes to the development of salt-sensitive hypertension. Endothelial NO synthase knockout (eNOS KO; total n = 64) and wild-type (WT; total n = 58) mice were given diets containing either normal (NS; 0.4%) or high-salt (HS; 4%) for 2 wk. During this period, mice were chronically treated with a O2− scavenger, tempol (400 mg/l), or an inhibitor of NADPH oxidase, apocynin (1 g/l), in drinking water or left untreated ( n = 6–8 per group). Blood pressure was measured by radiotelemetry and 24-h urine samples were collected in metabolic cages. Basal mean arterial pressure (MAP) in eNOS KO was higher (125 ± 4 vs. 106 ± 3 mmHg) compared with WT. Feeding HS diet did not alter MAP in WT but increased it in eNOS KO to 166 ± 9 mmHg. Both tempol and apocynin treatment significantly attenuated the MAP response to HS in eNOS KO (134 ± 3 and 139 ± 4 mmHg, respectively). Basal urinary 8-isoprostane excretion rates (UIsoV), a marker for endogenous O2− activity, were similar (2.8 ± 0.2 and 2.4 ± 0.3 ng/day) in both eNOS KO and WT mice. However, HS increased UIsoV more in eNOS KO than in WT (4.6 ± 0.3 vs. 3.8 ± 0.2 ng/day); these were significantly attenuated by both tempol and apocynin treatment. These data indicate that an enhancement in O2− activity contributes substantially to the development of salt-sensitive hypertension under NO-deficient conditions.

scholarly journals Role of Rho in Salt-Sensitive Hypertension

2021 ◽  
Vol 22 (6) ◽  
pp. 2958
Author(s):  
Wakako Kawarazaki ◽  
Toshiro Fujita
Keyword(s):  
Intracellular Signaling ◽  
Salt Intake ◽  
Rho Kinase ◽  
Renin Angiotensin System ◽  
High Salt ◽  
No Production ◽  
Nucleotide Exchange ◽  
High Salt Intake ◽  
Guanosine Triphosphatase ◽  
Salt Sensitive Hypertension

A high amount of salt in the diet increases blood pressure (BP) and leads to salt-sensitive hypertension in individuals with impaired renal sodium excretion. Small guanosine triphosphatase (GTP)ase Rho and Rac, activated by salt intake, play important roles in the pathogenesis of salt-sensitive hypertension as key switches of intracellular signaling. Focusing on Rho, high salt intake in the central nervous system increases sodium concentrations of cerebrospinal fluid in salt-sensitive subjects via Rho/Rho kinase and renin-angiotensin system activation and causes increased brain salt sensitivity and sympathetic nerve outflow in BP control centers. In vascular smooth muscle cells, Rho-guanine nucleotide exchange factors and Rho determine sensitivity to vasoconstrictors such as angiotensin II (Ang II), and facilitate vasoconstriction via G-protein and Wnt pathways, leading to increased vascular resistance, including in the renal arteries, in salt-sensitive subjects with high salt intake. In the vascular endothelium, Rho/Rho kinase inhibits nitric oxide (NO) production and function, and high salt amounts further augment Rho activity via asymmetric dimethylarginine, an endogenous inhibitor of NO synthetase, causing aberrant relaxation and increased vascular tone. Rho-associated mechanisms are deeply involved in the development of salt-sensitive hypertension, and their further elucidation can help in developing effective protection and new therapies.

Role of endothelin ETB receptor activation in angiotensin II-induced hypertension: effects of salt intake

2001 ◽  
Vol 281 (5) ◽  
pp. H2218-H2225 ◽  
Author(s):  
Jennifer R. Ballew ◽  
Gregory D. Fink
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Salt Intake ◽  
Receptor Activation ◽  
Salt Sensitivity ◽  
Male Rats ◽  
Ang Ii ◽  
High Salt Intake ◽  
Induced Hypertension

We showed recently that endothelin (ET)A receptors are involved in the salt sensitivity of ANG II-induced hypertension. The objective of this current study was to characterize the role of endothelin ETB receptor activation in the same model. Male rats on fixed normal (2 meq/day) or high (6 meq/day) salt intake received a continuous intravenous infusion of ANG II or salt only for 15 days. During the middle 5 days of the infusion period, rats were given either the selective ETB receptor antagonist A-192621 or the nonselective endothelin receptor antagonist A-182086 (both at 24 mg · kg−1 · day−1intra-arterially). Infusion of ANG II caused a greater rise in arterial pressure in rats on high-salt intake. The administration of A-192621 increased arterial pressure further in all rats. The chronic hypertensive effect of A-192621 was not significantly affected by salt intake or ANG II. The administration of A-182086 lowered arterial pressure chronically only in rats on normal salt intake receiving ANG II. Thus the salt sensitivity of ANG II-induced hypertension is not caused by changes in ETB receptor function.

Salt sensitivity in experimental thyroid disorders in rats

2011 ◽  
Vol 301 (2) ◽  
pp. E281-E287 ◽  
Author(s):  
Rocío Perez-Abud ◽  
Isabel Rodríguez-Gómez ◽  
Ana Belén Villarejo ◽  
Juan Manuel Moreno ◽  
Rosemary Wangensteen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Thyroid Disorders ◽  
High Salt Intake ◽  
Male Wistar Rats ◽  
Experimental Thyroid ◽  
And Oxidative Stress

This study assessed salt sensitivity, analyzing the effects of an increased saline intake on hemodynamic, morphological, and oxidative stress and renal variables in experimental thyroid disorders. Six groups of male Wistar rats were used: control, hypothyroid, hyperthyroid, and the same groups treated with salt (8% via food intake). Body weight, blood pressure (BP), and heart rate (HR) were recorded weekly for 6 wk. Finally, BP and HR were recorded directly, and morphological, metabolic, plasma, and renal variables were measured. High-salt intake increased BP in thyroxine-treated rats but not in control or hypothyroid rats. High-salt intake increased cardiac mass in all groups, with a greater increase in hyperthyroid rats. Urinary isoprostanes and H2O2 were higher in hyperthyroid rats and were augmented by high-salt intake in all groups, especially in hyperthyroid rats. High-salt intake reduced plasma thyroid hormone levels in hyperthyroid rats. Proteinuria was increased in hyperthyroid rats and aggravated by high-salt intake. Urinary levels of aminopeptidases (glutamyl-, alanyl-, aspartyl-, and cystinylaminopeptidase) were increased in hyperthyroid rats. All aminopeptidases were increased by salt intake in hyperthyroid rats but not in hypothyroid rats. In summary, hyperthyroid rats have enhanced salt sensitivity, and high-salt intake produces increased BP, cardiac hypertrophy, oxidative stress, and signs of renal injury. In contrast, hypothyroid rats are resistant to salt-induced BP elevation and renal injury signs. Urinary aminopeptidases are suitable biomarkers of renal injury.

scholarly journals Salt-sensitive splice variant of nNOS expressed in the macula densa cells

2010 ◽  
Vol 298 (6) ◽  
pp. F1465-F1471 ◽  
Author(s):  
Deyin Lu ◽  
Yiling Fu ◽  
Arnaldo Lopez-Ruiz ◽  
Rui Zhang ◽  
Ramiro Juncos ◽  
...  
Keyword(s):  
Salt Intake ◽  
Splice Variants ◽  
Macula Densa ◽  
High Salt ◽  
Tubuloglomerular Feedback ◽  
No Production ◽  
Thick Ascending Limb ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake

Neuronal nitric oxide synthase (nNOS), which is abundantly expressed in the macula densa cells, attenuates tubuloglomerular feedback (TGF). We hypothesize that splice variants of nNOS are expressed in the macula densa, and nNOS-β is a salt-sensitive isoform that modulates TGF. Sprague-Dawley rats received a low-, normal-, or high-salt diet for 10 days and levels of the nNOS-α, nNOS-β, and nNOS-γ were measured in the macula densa cells isolated with laser capture microdissection. Three splice variants of nNOS, α-, β-, and γ-mRNAs, were detected in the macula densa cells. After 10 days of high-salt intake, nNOS-α decreased markedly, whereas nNOS-β increased two- to threefold in the macula densa measured with real-time PCR and in the renal cortex measured with Western blot. NO production in the macula densa was measured in the perfused thick ascending limb with an intact macula densa plaque with a fluorescent dye DAF-FM. When the tubular perfusate was switched from 10 to 80 mM NaCl, a maneuver to induce TGF, NO production by the macula densa was increased by 38 ± 3% in normal-salt rats and 52 ± 6% ( P < 0.05) in the high-salt group. We found 1) macula densa cells express nNOS-α, nNOS-β, and nNOS-γ, 2) a high-salt diet enhances nNOS-β, and 3) TGF-induced NO generation from macula densa is enhanced in high-salt diet possibly from nNOS-β. In conclusion, we found that the splice variants of nNOS expressed in macula densa cells were α-, β-, and γ-isoforms and propose that enhanced level of nNOS-β during high-salt intake may contribute to macula densa NO production and help attenuate TGF.

scholarly journals High Salt Intake Increases Copeptin but Salt Sensitivity Is Associated with Fluid Induced Reduction of Copeptin in Women

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Irina Tasevska ◽  
Sofia Enhörning ◽  
Philippe Burri ◽  
Olle Melander
Keyword(s):  
Body Weight ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Dietary Salt ◽  
Urinary Volume ◽  
Salt Consumption ◽  
High Salt Intake ◽  
Low Salt ◽  
Induced Changes

This study investigated if copeptin is affected by high salt intake and whether any salt-induced changes in copeptin are related to the degree of salt sensitivity. The study was performed on 20 men and 19 women. In addition to meals containing 50 mmol NaCl daily, capsules containing 100 mmol NaCl and corresponding placebo capsules were administered during 4 weeks each, in random order. Measurements of 24 h blood pressure, body weight, 24 h urinary volume, and fasting plasma copeptin were performed at high and low salt consumption. Copeptin increased after a high compared to low dietary salt consumption in all subjects 3,59 ± 2,28 versus 3,12 ± 1,95 (P= 0,02). Copeptin correlated inversely with urinary volume, at both low (r= −0,42;P= 0,001) and high (r= −0,60;P< 0,001) salt consumption, as well as with the change in body weight (r= −0,53;P< 0,001). Systolic salt sensitivity was inversely correlated with salt-induced changes of copeptin, only in females (r= −0,58;P= 0,017). As suppression of copeptin on high versus low salt intake was associated with systolic salt sensitivity in women, our data suggest that high fluid intake and fluid retention may contribute to salt sensitivity.

scholarly journals Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats

2009 ◽  
Vol 296 (4) ◽  
pp. R994-R1000 ◽  
Author(s):  
Bing S. Huang ◽  
Roselyn A. White ◽  
Arco Y. Jeng ◽  
Frans H. H. Leenen
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Aldosterone Synthase ◽  
High Salt Intake ◽  
Induced Hypertension ◽  
Synthase Inhibitor ◽  
The Brain

In Dahl salt-sensitive (S) rats, high salt intake increases cerebrospinal fluid (CSF) Na+ concentration ([Na+]) and blood pressure (BP). Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR) blocker prevents the hypertension. To assess the role of aldosterone locally produced in the brain, we evaluated the effects of chronic central blockade with the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on changes in aldosterone and corticosterone content in the hypothalamus and the increase in CSF [Na+] and hypertension induced by high salt intake in Dahl S rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were not changed, but hypothalamic aldosterone increased by ∼35% and corticosterone tended to increase in Dahl S rats, whereas both steroids decreased by ∼65% in Dahl salt-resistant rats. In Dahl S rats fed the high-salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase in CSF [Na+]. ICV infusion of FAD286 prevented the increase in hypothalamic aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake. ICV infusion of spironolactone fully prevented the salt-induced hypertension. These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension.

scholarly journals Epithelial Sodium Channel and Salt-Sensitive Hypertension

Hypertension ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 759-767
Author(s):  
Stephanie M. Mutchler ◽  
Annet Kirabo ◽  
Thomas R. Kleyman
Keyword(s):  
Blood Pressure ◽  
Sodium Channel ◽  
Salt Intake ◽  
Extracellular Fluid ◽  
Pressure Rise ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
High Salt Intake ◽  
Salt Sensitive Hypertension

The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.

scholarly journals High Salt Intake Augments Excitability of PVN Neurons in Rats: Role of the Endoplasmic Reticulum Ca2+ Store

2017 ◽  
Vol 11 ◽  
Author(s):  
Robert A. Larson ◽  
Andrew D. Chapp ◽  
Le Gui ◽  
Michael J. Huber ◽  
Zixi Jack Cheng ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Salt Intake ◽  
High Salt ◽  
High Salt Intake
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