Abstract P217: Imbalance Of M1/M2 Macrophages In Ovaries Of Hypertensive Mice Is Associated With Reproductive Dysfunction And Lymphangiogenesis

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Shobana Navaneethabalakrishnan ◽  
Brooke K Wilcox ◽  
Bethany L Goodlett ◽  
Brett M Mitchell
Keyword(s):  
Gene Expression ◽  
Hormone Receptors ◽  
Tap Water ◽  
Systemic Circulation ◽  
Normal Diet ◽  
M2 Macrophages ◽  
High Salt Diet ◽  
Reproductive Dysfunction ◽  
Therapeutic Opportunity ◽  
Salt Sensitive Hypertension

Macrophages are the principal immune cells in ovaries. Besides protecting against invading pathogens and antigens, macrophages also play an essential role in folliculogenesis, ovulation, luteinization, lymphangiogenesis, and other functions. An imbalance in M1/M2 macrophages is observed in systemic circulation in patients and animals with hypertension (HTN). Although studies have demonstrated an association between HTN and reproductive dysfunction in females, the effect of HTN on ovarian M1/M2 ratio and lymphatics is largely unknown. We hypothesized that L-NAME-induced HTN (LHTN) and salt-sensitive hypertension (SSHTN) may increase the M1/M2 balance in ovaries which is associated with lymphangiogenesis and reproductive dysfunction in mice. Female mice were either provided L-NAME (0.5 mg/mL) in their drinking water for 3 weeks or L-NAME for 2 weeks, followed by a 2-week washout period and subsequent 3-week 4% high salt diet (SSHTN). Control mice (C) received tap water and normal diet. Flow cytometry analysis revealed a significant decrease in M1 (C: 46%±1, LHTN: 33%±2; p<0.05) and an increase in M2 (C: 7%±1, LHTN: 12%±1; p<0.05) macrophages in ovaries from LHTN mice. In SSHTN mice, ovaries had significantly increased M1 (C: 24%±1, SSHTN: 44%±2; p<0.05) and decreased M2 (C: 12%±1, SSHTN: 4%±1; p<0.05) macrophages. There was a significant increase in gene expression of the hormone receptors AR, FSHR, ERa, ERb, and LHR, and the steroidogenic enzymes StAR, 3bHSD, CYP11a1, and CYP17a1. Ovaries of hypertensive mice had a significant increase in gene expression of the lymphatic vessel markers Lyve-1, Podoplanin, and Prox-1, the lymphangiogenic growth factor VEGF-C and receptors VEGFR-2 and VEGFR-3. Taken together these data demonstrate that HTN disturbs M1/M2 macrophages in ovaries and is associated with reproductive dysfunction and lymphangiogenesis. Manipulation of M1/M2 ratio may be a therapeutic opportunity to improve reproductive health in hypertensive women.

Abstract 16: Altered Testicular Macrophage Polarization Is Associated With Reproductive Dysfunction In Hypertensive Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Shobana Navaneethabalakrishnan ◽  
Brooke K Wilcox ◽  
Bethany L Goodlett ◽  
Brett M Mitchell
Keyword(s):  
Gene Expression ◽  
Reproductive Health ◽  
Hormone Receptors ◽  
Tap Water ◽  
Macrophage Polarization ◽  
Sperm Concentration ◽  
Mitochondrial Activity ◽  
Reproductive Dysfunction ◽  
The Impact ◽  
Testicular Macrophages

Elevated circulating proinflammatory (M1) and decreased anti-inflammatory (M2) macrophages contribute to hypertension (HTN) and end-organ damage. HTN is associated with reproductive dysfunction in men. However, the impact of HTN on testicular macrophages and inflammation is unknown. We hypothesized that HTN increases M1 and decreases M2 testicular macrophages, which is associated with inflammation and reproductive dysfunction. Male mice were made hypertensive by either providing L-arginine methyl ester hydrochloride (L-NAME) (0.5 mg/mL) in the drinking water for 3 weeks [L-NAME-induced HTN (LHTN)] or L-NAME water for 2 weeks, followed by a 2-week washout period and a subsequent 3-week 4% high salt diet [salt-sensitive hypertension (SSHTN)]. Control (C) mice received tap water and normal diet. Flow cytometry analysis revealed a significant increase in both M1 (C: 15%±1, LHTN: 22%±2; p<0.05) and M2 (C: 10%±1, LHTN: 21%±2; p<0.05) macrophages in testes from LHTN mice. Similarly, testes from SSHTN mice had a significant increase in M1 (C: 17%±1, SSHTN: 28%±2; p<0.05) but had a significant decrease in M2 (C: 14%±1, SSHTN: 7%±1; p<0.05) macrophages. Testes from both hypertension models had a significant increase in gene expression of the proinflammatory cytokines TNFa, IFNg, IL-1b, IL-6, and IL-17. Sperm concentration (C: 8.5±0.7, LHTN: 6.5±0.2, SSHTN: 4.7±0.5; both p<0.05) and the percentage of sperm mitochondrial activity (C: 88%±3, LHTN: 71±5, SSHTN: 64%±3; both p<0.05) were decreased significantly in both hypertension groups. Hypertensive mice presented a significantly increased percentage of sperm with abnormal morphology (C: 5%±1, LHTN: 8%±1, SSHTN: 13%±2; both p<0.05) and damaged acrosome (C: 1.4%±0.2, LHTN: 2.8%±0.2, SSHTN: 4%±0.5; both p<0.05). There was a significant decrease in gene expression of the hormone receptors AR, ERa, and LHR, and the steroidogenic enzymes StAR, 3bHSD, 17bHSD, and CYP17a1 in the testes of LHTN and SSHTN mice. These data demonstrate that HTN alters testicular macrophage polarization which is associated with inflammation and impaired reproductive health. Therapeutic strategies may be developed to improve reproductive health in male hypertensive patients by targeting testicular macrophage imbalance.

scholarly journals Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2

2008 ◽  
Vol 295 (2) ◽  
pp. F462-F470 ◽  
Author(s):  
Peijun P. Shi ◽  
Xiao R. Cao ◽  
Eileen M. Sweezer ◽  
Thomas S. Kinney ◽  
Nathan R. Williams ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Normal Diet ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Ww Domains ◽  
Salt Sensitive Hypertension

Nedd4-2 has been proposed to play a critical role in regulating epithelial Na+ channel (ENaC) activity. Biochemical and overexpression experiments suggest that Nedd4-2 binds to the PY motifs of ENaC subunits via its WW domains, ubiquitinates them, and decreases their expression on the apical membrane. Phosphorylation of Nedd4-2 (for example by Sgk1) may regulate its binding to ENaC, and thus ENaC ubiquitination. These results suggest that the interaction between Nedd4-2 and ENaC may play a crucial role in Na+ homeostasis and blood pressure (BP) regulation. To test these predictions in vivo, we generated Nedd4-2 null mice. The knockout mice had higher BP on a normal diet and a further increase in BP when on a high-salt diet. The hypertension was probably mediated by ENaC overactivity because 1) Nedd4-2 null mice had higher expression levels of all three ENaC subunits in kidney, but not of other Na+ transporters; 2) the downregulation of ENaC function in colon was impaired; and 3) NaCl-sensitive hypertension was substantially reduced in the presence of amiloride, a specific inhibitor of ENaC. Nedd4-2 null mice on a chronic high-salt diet showed cardiac hypertrophy and markedly depressed cardiac function. Overall, our results demonstrate that in vivo Nedd4-2 is a critical regulator of ENaC activity and BP. The absence of this gene is sufficient to produce salt-sensitive hypertension. This model provides an opportunity to further investigate mechanisms and consequences of this common disorder.

scholarly journals Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2− and is diminished by a high-salt diet

2004 ◽  
Vol 287 (2) ◽  
pp. F224-F230 ◽  
Author(s):  
Marisela Varela ◽  
Marcela Herrera ◽  
Jeffrey L. Garvin
Keyword(s):  
Atpase Activity ◽  
Cultured Cells ◽  
Atp Hydrolysis ◽  
Tap Water ◽  
Normal Diet ◽  
High Salt ◽  
Thick Ascending Limb ◽  
High Salt Diet ◽  
Effect Change ◽  
Salt Diet

A high-salt diet enhances nitric oxide (NO)-induced inhibition of transport in the thick ascending limb (THAL). Long exposures to NO inhibit Na-K-ATPase in cultured cells. We hypothesized that NO inhibits THAL Na-K-ATPase after long exposures and a high-salt diet would augment this effect. Rats drank either tap water or 1% NaCl for 7–10 days. Na-K-ATPase activity was assessed by measuring ouabain-sensitive ATP hydrolysis by THAL suspensions. After 2 h, spermine NONOate (SPM; 5 μM) reduced Na-K-ATPase activity from 0.44 ± 0.03 to 0.30 ± 0.04 nmol Pi·μg protein−1·min−1 in THALs from rats on a normal diet ( P < 0.03). Nitroglycerin also reduced Na-K-ATPase activity ( P < 0.04). After 20 min, SPM had no effect (change −0.07 ± 0.05 nmol Pi·μg protein−1·min−1). When rats were fed high salt, SPM did not inhibit Na-K-ATPase after 120 min. To investigate whether ONOO− formed by NO reacting with O2− was involved, we measured O2− production. THALs from rats on normal and high salt produced 35.8 ± 0.3 and 23.7 ± 0.8 nmol O2−·min−1·mg protein−1, respectively ( P < 0.01). Because O2− production differed, we studied the effects of the O2− scavenger tempol. In the presence of 50 μM tempol, SPM did not inhibit Na-K-ATPase after 120 min (0.50 ± 0.05 vs. 0.52 ± 0.07 nmol Pi·μg protein−1·min−1). Propyl gallate, another O2− scavenger, also prevented SPM-induced inhibition of Na-K-ATPase activity. SPM inhibited pump activity in tubules from rats on high salt when O2− levels were increased with xanthine oxidase and hypoxanthine. We concluded that NO inhibits Na-K-ATPase after long exposures when rats are on a normal diet and this inhibition depends on O2−. NO donors do not inhibit Na-K-ATPase in THALs from rats on high salt due to decreased O2− production.

Abstract 11005: Activation of Hypothalamic Mineralocorticoid Receptor-Independent Epithelial Sodium Channels Leads to Salt-Sensitive Hypertension in Mouse Model of Metabolic Syndrome

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Mutsumi Kunita-Takanezawa ◽  
Koji Ito ◽  
Takuya Kishi ◽  
Yoshitaka Hirooka
Keyword(s):  
Metabolic Syndrome ◽  
Mineralocorticoid Receptor ◽  
Tap Water ◽  
Urinary Sodium Excretion ◽  
Normal Diet ◽  
Salt Loading ◽  
Intracerebroventricular Infusion ◽  
Induced Hypertension ◽  
Plasma Arginine ◽  
Salt Sensitive Hypertension

Introduction and Hypothesis: Metabolic syndrome (MetS) is often associated with salt-sensitive hypertension. In genetic salt-sensitive hypertensive models, activation of the hypothalamic mineralocorticoid receptor (MR)-epithelial sodium channel (ENaC) pathway has been established as a major worsening factor. However, in MetS, contribution of the hypothalamic MR-ENaC pathway to salt-sensitive hypertension remains unknown. Therefore, we determined whether the hypothalamic MR-ENaC pathway activation leads to salt-sensitive hypertension in MetS. Methods and Results: Diet-induced obesity (DIO) was achieved in male C57BL/6 mice by feeding them a high-fat diet from 4 weeks of age. Mice fed a normal diet served as controls (CON). Mice at 12 weeks of age were given tap water with regular salt (RS) or 1% NaCl (high salt; HS) for 8 weeks. HS led to increased systolic blood pressure only in DIO-mice, and not in CON-mice (DIO-HS: 122±3 mmHg vs DIO-RS: 107±2 mmHg, CON-HS: 109±2 mmHg vs CON-RS: 105±1 mmHg, n=6/group, p<0.05). In DIO-mice, 24-h urinary norepinephrine excretion after salt loading was significantly higher than that before salt loading (244±18 ng/day vs 371±29 ng/day, n=6 in each, p<0.05). HS-induced hypertension was significantly prevented by intracerebroventricular infusion of the ENaC blocker benzamil (Ben), but not the MR blocker spironolactone (Spl; DIO-HS-Vehicle 122±1 mmHg, DIO-HS-Ben 108±1 mmHg, DIO-HS-Spl 119±1 mmHg, n=6 in each, p<0.05). Expression of hypothalamic serum and glucocorticoid-regulated kinase (SGK) 1, a marker of MR activity, did not differ between in CON-mice and DIO-mice. However, the SGK1 phosphorylation level was greater in DIO-mice than in CON-mice, suggesting MR-independent SGK1 activation. Water intake and urinary sodium excretion did not differ between in DIO-HS-Vehicle and DIO-HS-Ben. Interestingly, salt loading-induced plasma arginine vasopressin (AVP) secretion was significantly prevented in DIO-HS-Ben. Conclusions: These findings suggest that salt-induced hypertension in DIO-mice results from MR-independent hypothalamic SGK1-ENaC activation with systemic AVP secretion. Hypothalamic ENaC could be a novel therapeutic target in salt-induced hypertension of MetS.

Microarray Analysis of Gene Expression in the Renal Inner Medulla of the Dahl Salt-Resistant and Salt-Sensitive Rat

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 686-686
Author(s):  
Robert W Jackson ◽  
David M Pollock ◽  
Terry R Stoming ◽  
Jennifer S Pollock
Keyword(s):  
Gene Expression ◽  
Adaptive Response ◽  
Transcriptional Response ◽  
High Salt ◽  
Atpase Inhibitor ◽  
High Salt Diet ◽  
High Sodium ◽  
Renal Inner Medulla ◽  
Salt Sensitive Hypertension ◽  
High Sodium Diet

49 The inner medulla contains several mechanisms that play a central role in fluid-volume homeostasis. We hypothesized that transcriptional regulation of the inner medulla in response to a high sodium diet differs between the Dahl salt-resistant (SR) and salt-sensitive (SS) rats. SR and SS (16 wk) were placed on either a 0.5% (low) or 4.0% (high) NaCl diet. After 5 weeks, total RNA from the renal inner medulla was isolated from two rats in each of the following groups: SR/low, SR/high, SS/low, and SS/high. Labeled cRNA was hybridized to microarrays representing 7000 genes (Affymetrix). In response to increased Na intake in the SR rat, 46 genes were up-regulated and 7 genes down-regulated (>2-fold changes). This adaptive response included the up-regulation of guanylin (3-fold;3X), cytochrome P 450 (8X), cyclooxygenase-2 (3X), kidney-specific androgen-regulated protein (8X) and the down regulation of Tamm-Horsfall protein (-39X). In contrast, high salt in SS rats revealed the differential expression of only one gene, the up-regulation of guanylin (3X). To investigate the general absence of a transcriptional response in SS rats, we found that, 23 genes were expressed at higher levels and 14 at lower levels in SS/low compared to SR/low. Interestingly, 7 of 23 genes that were elevated in the SS/low, were the same genes that were up-regulated in the SR/high. Thus, components of the adaptive response to high Na in SR rats are operating in SS rats prior to a Na challenge. Ten genes were increased and four were decreased in the SS/high when compared to the SR/high. The ROMK K + channel (3X), Na-K-2Cl cotransporter (6X), and an ATPase inhibitor (8X) were expressed at higher levels in the SS/high. A majority of the other genes not mentioned have not been studied in the context of sodium handling or hypertension. These findings reveal clear differences in the basal gene expression within the inner medulla between SR and SS rats. Furthermore, these results show that salt-sensitivity is associated with a diminished transcriptional response to a high salt diet which supports the hypothesis that this region of the kidney contributes to genetic salt-sensitive hypertension.

scholarly journals Dietary Fructose Increases the Sensitivity of Proximal Tubules to Angiotensin II in Rats Fed High-Salt Diets

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1244 ◽  
Author(s):  
Agustin Gonzalez-Vicente ◽  
Nancy Hong ◽  
Nianxin Yang ◽  
Pablo Cabral ◽  
Jessica Berthiaume ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Tap Water ◽  
Transport Processes ◽  
High Salt ◽  
Proximal Tubules ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Fructose ◽  
Salt Sensitive Hypertension

Dietary fructose causes salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the filtered NaCl. Angiotensin II (Ang II), atrial natriuretic peptide (ANP) and norepinephrine (NE) regulate this process. Although Ang II signaling blockade ameliorates fructose-induced salt-sensitive hypertension, basal PT Na+ reabsorption and its sensitivity to the aforementioned factors have not been studied in this model. We hypothesized consuming fructose with a high-salt diet selectively enhances the sensitivity of PT transport to Ang II. We investigated the effects of Ang II, ANP and NE on PT Na reabsorption in rats fed a high-salt diet drinking tap water (HS) or 20% fructose (HS-FRU). Oxygen consumption (QO2) was used as a measure of all ATP-dependent transport processes. Na+/K+-ATPase and Na+/H+-exchange (NHE) activities were studied because they represent primary apical and basolateral transporters in this segment. The effect of 10−12 mol/L Ang II in QO2 by PTs from HS-FRU was larger than HS (p < 0.02; n = 7). In PTs from HS-FRU 10−12 mol/L Ang II stimulated NHE activity by 2.6 ± 0.7 arbitrary fluorescence units/s (p < 0.01; n = 5) but not in those from HS. The stimulatory effect of Ang II on PT Na+/K+-ATPase activity was not affected by HS-FRU. Responses of QO2 and NHE activity to ANP did not differ between groups. The response of QO2 to NE was unaltered by HS-FRU. We concluded that the sensitivity of PT Na+ reabsorption specifically to Ang II is enhanced by HS-FRU. This maintains high rates of transport even in the presence of low concentrations of the peptide, and likely contributes to the hypertension.

Abstract 098: Augmenting Renal Lymphatic Vessel Density Prevents Salt-sensitive Hypertension in Mice

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Dakshnapriya Balasubbramanian ◽  
Catalina A Lopez Gelston ◽  
Gabriella R Abouelkheir ◽  
Alexandra H Lopez ◽  
Kayla R Hudson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymphatic Vessel ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
High Salt ◽  
Vessel Density ◽  
Lymphatic Vessel Density ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

Salt-sensitive hypertension (SSHTN) is associated with renal immune cell infiltration and interstitial inflammation. Lymphatic vessels drain the interstitial compartment and traffic immune cells to draining lymph nodes; however little is known about the role of lymphatics and immune cell trafficking in the kidney during SSHTN. Our hypotheses were that renal lymphatic vessel density is increased in mice with SSHTN and that further augmenting renal lymphatic vessels will prevent SSHTN. SSHTN mice were made by administering L-NAME for two weeks, followed by a two week washout, and then were fed a 4% high salt diet for three weeks. Compared to control mice, mice with SSHTN (SBP: 103±3 vs. 136±2 mmHg; p<0.05) had markedly increased renal lymphatic vessel density. Kidneys of SSHTN mice had significantly increased gene expression of the lymphatic vessel marker Lyve1 , the macrophage marker Adgre1 (F4/80), the Th1 cell marker Tbx21 , and the pro-inflammatory cytokine Il6 while expression of the immune cell-lymphatic chemokine receptor Ccr7 was decreased significantly. Mice solely fed a 4% salt diet for three weeks did not exhibit hypertension or increased renal lymphatic vessel density. To determine whether augmenting renal lymphatic vessels prior to the high salt diet could prevent SSHTN, we used transgenic mice that overexpress the lymphangiogenic signal VEGF-D only in the kidney under the control of doxycycline (KidVD+ mice) and thus exhibit renal lymphangiogenesis. Doxycycline initiated one week prior to the high salt diet prevented SSHTN in KidVD+ mice while having no effect on blood pressure in KidVD- mice (SBP: 117±4 vs. 139±5 mmHg; p<0.05). Renal gene expression of Tbx21 was decreased in KidVD+ mice while Ccr7 gene expression was increased significantly. These data demonstrate that renal lymphatic vessel density is increased in SSHTN and that augmenting renal lymphatic vessel density prior to a high salt diet can prevent SSHTN by improving renal immune cell exfiltration.

Reparação óssea no implante dental

2020 ◽  
Vol 12 (45) ◽  
pp. 63-66
Author(s):  
Halim Nagem Filho ◽  
Reinaldo Francisco Maia ◽  
Reinaldo Missaka ◽  
Nasser Hussein Fares
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Close Contact ◽  
The Other ◽  
Main Function ◽  
Indirect Interaction ◽  
M2 Macrophages ◽  
Activated Macrophages ◽  
M1 Macrophages ◽  
High Production

The osseointegration is the stable and functional union between the bone and a titanium surface. A new bone can be found on the surface of the implant about 1 week after its installation; the bone remodeling begins between 6 and 12 weeks and continues throughout life. After the implant insertion, depending on the energy of the surface, the plasma fluid immediately adheres, in close contact with the surface, promoting the adsorption of proteins and inducing the indirect interaction of the cells with the material. Macrophages are cells found in the tissues and originated from bone marrow monocytes. The M1 macrophages orchestrate the phagocytic phase in the inflammatory region and also produce inflammatory cytokines involved with the chronic inflammation and the cleaning of the wound and damaged tissues from bacteria. On the other hand, alternative-activated macrophages (M2) are activated by IL-10, the immune complex. Its main function consists on regulating negatively the inflammation through the secretion of the immunosuppressant IL-10. The M2 macrophages present involvement with the immunosuppression, besides having a low capacity for presenting antigens and high production of cytokines; these can be further divided into M2a, M2b, and M2c, based on the gene expression profile.

scholarly journals Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

2019 ◽  
Vol 20 (14) ◽  
pp. 3495 ◽  
Author(s):  
Yanling Yan ◽  
Jiayan Wang ◽  
Muhammad A. Chaudhry ◽  
Ying Nie ◽  
Shuyan Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Significant Rise ◽  
Protein Carbonylation ◽  
High Salt ◽  
Kidney Cortex ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

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