Abstract 275: The Effect of High Salt-diet on Pioglitazone Treated-db/db-/- mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Patience O Obih ◽  
Michael C Ezebuenyi ◽  
Akeem P Jimoh ◽  
John-Clifford A Obih
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Physiological Saline ◽  
Experimental Period ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood ◽  
Sodium Load ◽  
The Impact

The objective of this study was to evaluate the impact of high-salt-diet on pioglitazone treated db/db mice. Groups of 6 weeks-old db/db mice obtained from Jackson Laboratory were given either pioglitazone (0.02%) in diet or pioglitazone (0.02%) plus high salt-diet (8% NaCl) for 6 to 12 weeks. Control groups received either pioglitazone or normal salt diet. During the course of treatment, urine volume, urine sodium, creatinine and blood glucose were measured in the animals. For urine collection, mice were placed in metabolic cages. In order to evaluate whether differences exist between diabetic animals that received pioglitazone or not in the handling of a sodium load and to characterize the transport mechanisms involved, at the end of experimental period the animals were given an acute sodium load (physiological saline), 1.25 ml/100 g body weight by intraperitoneal route. The sodium load was repeated in mice that was treated 15 minutes earlier with hydrochlorothiazide (40 mg/kg i.p.) or furosemide (8 mg/kg i.p.), or amiloride (1.65 mg/kg). The animals were placed in metabolic cages and urine voided was collected over 5 hr. for determination of urine volume and sodium. Sodium was determined by flame photometer. No significant changes were observed in mean arterial blood pressure in all the groups (at p 0.05). There was significant increase in UNav with all the diuretics in db/db mice that received high salt diet at 6 weeks. The blood pressure did not increase with the sodium diet. This might be due to natriuresis resulting from polyurea in the diabetic condition of the mice.

Effects of a chronic high-salt diet on large artery structure: role of endogenous bradykinin

1998 ◽  
Vol 274 (5) ◽  
pp. H1423-H1428 ◽  
Author(s):  
Chohreh Partovian ◽  
Athanase Benetos ◽  
Jean-Pierre Pommiès ◽  
Willy Mischler ◽  
Michel E. Safar
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Large Artery ◽  
High Salt Diet ◽  
Salt Diet ◽  
Wky Rats ◽  
Arterial Blood ◽  
Arterial Structure ◽  
Hoe 140

Bradykinin activity could explain the blood pressure increase during NaCl loading in hypertensive animals, but its contribution on vascular structure was not evaluated. We determined cardiac mass and large artery structure after a chronic, 4-mo, high-salt diet in combination with bradykinin B2-receptor blockade by Hoe-140. Four-week-old rats were divided into eight groups according to strain [spontaneously hypertensive rats (SHR) vs. Wistar-Kyoto (WKY) rats], diet (0.4 vs. 7% NaCl), and treatment (Hoe-140 vs. placebo). In WKY rats, a high-salt diet significantly increased intra-arterial blood pressure with minor changes in arterial structure independently of Hoe-140. In SHR, blood pressure remained stable but 1) the high-salt diet was significantly associated with cardiovascular hypertrophy and increased arterial elastin and collagen, and 2) Hoe-140 alone induced carotid hypertrophy. A high-salt diet plus Hoe-140 acted synergistically on carotid hypertrophy and elastin content in SHR, suggesting that the role of endogenous bradykinin on arterial structure was amplified in the presence of a high-salt diet.

scholarly journals Sex dependent compensatory mechanisms to preserve blood pressure homeostasis in PGI2 receptor deficient mice

2020 ◽  
Author(s):  
Soon Yew Tang ◽  
Seán T. Anderson ◽  
Hu Meng ◽  
Dimitra Sarantopoulou ◽  
Emanuela Ricciotti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oxidant Stress ◽  
High Salt ◽  
Prostaglandin E ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Female Mice ◽  
The Impact ◽  
Deficient Mice

AbstractInhibitors of microsomal prostaglandin E synthase-1 (mPges-1) are in the early phase of clinical development. Deletion of mPges-1 confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing prostaglandin (PG) E2, but increasing biosynthesis of prostacyclin (PGI2). In hyperlipidemic mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thrombogenesis, while suppression of PGE2 accounts for its anti-atherogenic effect. However, the impact of mPges-1 depletion on blood pressure (BP) in this setting remains unknown.To address how differential effects on PGE2 and PGI2 might modulate salt-evoked BP responses in the absence of mPges-1, we generated mice lacking the I prostanoid (Ipr) receptor or mPges-1 on a hyperlipidemic background caused by deletion of the low density lipoprotein receptor (Ldlr KOs). Here, mPges-1 depletion significantly increased the BP response to salt loading in male Ldlr KO mice, whereas, despite the direct vasodilator properties of PGI2, Ipr deletion suppressed it. Furthermore, combined deletion of the Ipr abrogated the exaggerated BP response in male mPges-1 KO mice. Suppression of PGE2 biosynthesis was enough to explain the exaggerated BP response to salt loading by either mPges-1/Ldlr depletion or by an MPGES-1 inhibitor in mice expressing human mPGES-1. However, the lack of a hypertensive response to salt in Ipr-deficient mice was attributable to reactive activation of the atrial natriuretic peptide pathway. Interestingly, these unexpected BP phenotypes were not observed in female mice fed a high salt diet. This is attributable to the protective effect of estrogen in Ldlr KO mice and in Ipr /Ldlr DKOs. Thus, estrogen compensates for a deficiency in PGI2 to maintain BP homeostasis in response to high salt in hyperlipidemic female mice. In males, by contrast, augmented formation of ANP plays a similar compensatory role, restraining hypertension and oxidant stress in the setting of Ipr depletion. Hyperlipidemic males on a high salt diet might be at risk of a hypertensive response to mPGES-1 inhibitors.

Orchidectomy attenuates impaired endothelial effects of a high-salt diet in Sprague–Dawley rats

2011 ◽  
Vol 89 (4) ◽  
pp. 295-304 ◽  
Author(s):  
A.K. Oloyo ◽  
O.A. Sofola ◽  
C.N. Anigbogu
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
High Salt ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension

The effect of sex hormones on vascular reactivity is considered one of the underlying factors contributing to gender differences in cardiovascular functions and diseases. Experiments were designed to investigate the role of androgens in salt-induced hypertension by assessing the relaxation response of isolated aortic rings to acetylcholine and sodium nitroprusside in the presence or absence of l-nitroarginine methyl ester in Sprague–Dawley rats. The rats were either orchidectomized or sham-operated, with or without testosterone replacement, and were placed on a normal or high-salt diet for 6 weeks. The results indicate a significant increase (p < 0.001) in the mean arterial blood pressure of rats on the high-salt diet, when compared with control or orchidectomized rats. Orchidectomy elicited a reduction in mean arterial blood pressure (p < 0.01), while testosterone replacement normalized mean arterial blood pressure to values seen in intact rats on the high-salt diet. The high-salt diet reduced the relaxation response to acetylcholine both in the presence and absence of inhibition of endothelial nitric oxide synthase with l-nitroarginine methyl ester. Bilateral orchidectomy attenuated the impaired endothelial function induced by the high-salt diet in rats, but this was reversed by concomitant administration of testosterone, suggesting a role for androgens in enhancing long-term vascular smooth muscle tone and hence maintenance of high blood pressure in salt-induced hypertension.

Abstract 478: Biological Pathways Mediating the Effect of a 1.37 Mbp Genomic Region on Salt-Induced Hypertension in the SS Rat

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Mingyu Liang ◽  
Chun Yang ◽  
Christine B Peterson ◽  
Pengyuan Liu ◽  
Francesco C Stingo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Graphical Models ◽  
Genomic Region ◽  
Biological Pathways ◽  
High Salt ◽  
Receptor Interaction ◽  
Rna Seq ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood

Previous analysis of 13 overlapping subcongenic strains led to the identification of a 1.37 Mbp region on chromosome 13 (positions 80.92 to 82.29 Mbp in the Rn5 genome assembly) that influenced the mean arterial blood pressure of the Dahl salt-sensitive (SS) rat on a high-salt diet by more than 20 mmHg. The goal of the present study was to identify biological pathways that could mediate the blood pressure effect of this genomic region. RNA-seq analysis was performed for the renal outer medulla tissue in five selected subcongenic strains, the SS, and a congenic strain from which the subcongenic strains were derived. Rats were fed a 0.4% salt diet or switched to a high-salt diet for 7 days. Affymetrix GeneChip data for SS and three additional congenic or consomic strains were obtained from a previous study. The RNA-seq and microarray data were merged using a cross-platform normalization method to generate a transcriptome dataset containing 90 observations for each gene. A Bayesian model analysis was performed for 243 biological pathways to assess their likelihood to discriminate blood pressure levels across experimental groups. Seven pathways showed posterior probabilities greater than 0.4. These pathways involved neuroactive ligand-receptor interaction, phenylalanine, tyrosine and tryptophan biosynthesis, and protein degradation. A Bayesian approach was used to estimate undirected graphical models among the three known genes located in the 1.37 Mbp region (Astn1, Fam5b, and Rfwd2) and genes in each of the 7 pathways identified above and 11 additional pathways known to be involved in blood pressure regulation. The analysis identified several previously unknown relationships between the three candidate genes and genes in pathways that could regulate blood pressure. The study demonstrated a new, unbiased approach for identifying biological pathways mediating the effect of a candidate genomic region on hypertension.

Abstract MP13: Etamicastat Prevents Arterial Blood Pressure Increase in Mice Lacking Salt-inducible Kinase 1 (SIK1)

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Nuno Pires ◽  
Bruno Igreja ◽  
Eduardo Moura ◽  
Maria João Bonifácio ◽  
Paula Serrão ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Renin Angiotensin System ◽  
Fold Increase ◽  
High Salt ◽  
High Salt Diet ◽  
Urinary Catecholamines ◽  
Salt Diet ◽  
Arterial Blood ◽  
High Salt Intake

Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic high-salt intake in mice (Circ Res 2015;116:642-52). Here, we address possible acute mechanisms that may relate to the observed high BP in mice lacking SIK1. SIK1 knockout ( sik1 -/- ) and wild-type ( sik1 +/+ ) littermate mice were challenged for seven days with a normal- (0.3% NaCl) or high-salt (8% NaCl) diet. Systolic BP (SBP) was significantly increased in sik1 -/- mice (137.0±17.2 mmHg) after seven days of high-salt intake, as compared to sik1 +/+ mice counterparts (120.6±4.5 mmHg). The renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) were assayed in order to investigate the possible causes for the increase in SBP in sik1 -/- mice fed a high-salt diet. No differences in renin (normal-salt: 463.4±17.9, high-salt: 462.9±28.9 pg/ml) and angiotensin II (normal-salt: 45.8±10.0, high-salt: 39.0±8.5 pg/ml) serum levels were observed. The activity of dopamine β-hydroxylase (DβH), the enzyme that converts dopamine (DA) to norepinephrine (NE), was significantly increased in the adrenal glands of sik1 -/- mice fed a high-salt diet (356.7±32.8 nmol/mg protein) as compared to sik1 -/- mice on a normal-salt diet (184.4±14.4 nmol/mg protein). Similarly, urinary catecholamines (DA, NE, epinephrine) and L-DOPA were significantly increased (3- to 7-fold increase) in sik1 -/- mice fed a high-salt diet as compared to sik1 -/- mice on a normal-salt intake. Altogether, this data supports the view that sik1 -/- mice fed a high-salt diet develop SNS overactivity. Next, we addressed the question if reducing SNS activity in sik1 -/- mice fed a high-salt diet would ameliorate hypertension. For that purpose, the effect of etamicastat, a peripheral reversible DβH inhibitor, was evaluated on the development of high BP upon high-salt diet. Etamicastat treatment (50 mg/kg/day), started prior to high-salt feeding, completely prevented SBP increase in sik1 -/- mice fed a high-salt diet (116.8±4.7 mmHg). It is concluded that the SNS is involved in the development of salt-induced hypertension in sik1 -/- mice and that the DβH inhibitor etamicastat is able to reduce SNS overactivity and high BP in this mouse model of hypertension.

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.

Endothelin B receptors impair baroreflex function and increase blood pressure variability during high salt diet

2021 ◽  
pp. 102796
Author(s):  
Bryan K. Becker ◽  
Jermaine G. Johnston ◽  
Carolyn Young ◽  
Alfredo A. Torres Rodriguez ◽  
Chunhua Jin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Variability ◽  
High Salt ◽  
Increase Blood Pressure ◽  
High Salt Diet ◽  
Salt Diet ◽  
Baroreflex Function ◽  
Endothelin B

Abstract 16835: Targeted Disruption of Paraoxonase 3 in a Dahl Salt-Sensitive Rat Model of Chronic Kidney Disease Increases Renal Cortical Pro-Inflammatory Eicosanoids

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Chrysan J Mohammed ◽  
Fatimah K Khalaf ◽  
Prabhatchandra Dube ◽  
Tyler J Reid ◽  
Jacob A Connolly ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
Renal Cortex ◽  
High Salt ◽  
High Density Lipoproteins ◽  
Wild Type ◽  
Targeted Disruption ◽  
High Salt Diet ◽  
Salt Diet ◽  
Mediators Of Inflammation

Background: Paraoxonase 3 (Pon3), is one of the three isoforms of the paraoxonase gene family. While Pon1 and Pon2 are widely studied, there is a paucity of knowledge regarding Pon3. Pon3 is synthesized in the liver and can circulate bound to high-density lipoproteins. There is significant expression in the kidney also. Pon3 has the ability to metabolize eicosanoids, which can act as signaling molecules and have known roles in the pathophysiology of some renal diseases. Decreased Pon activity is associated with elevated levels of eicosanoid metabolites and adverse clinical outcomes. We tested the hypothesis that targeted disruption of Pon3 results in elevated levels of pro-inflammatory eicosanoids and progression of renal injury. Methods/ Results: Ten week old male Dahl salt-sensitive (SS rats) and Pon3 mutant rats (SS Pon3 KO) were maintained on 8% high salt diet for eight weeks, to initiate salt-sensitive hypertensive renal disease. Previously we observed that SS Pon3 KO rats on eight weeks high salt diet demonstrated significantly increased phenotypic renal injury and mortality. In the current study, we noted that SS Pon3 KO had significantly decreased (p<0.05) glomerular filtration rate compared to SS wild type. Blood pressure (radiotelemetry) as well as plasma angiotensin and aldosterone (LC-MS/MS) were not different between the two groups after high salt diet. We used targeted lipidomic profiling to determine eicosanoid content in renal cortex from SS Pon3 KO and SS wild type rats at the end of eight weeks of high salt diet. We found that hydroxyl fatty acids 5-HEPE and 5-HETE (5-lipoxygenase dependent arachidonic acid metabolites) were significantly (p<0.05) elevated in the renal cortex of SS Pon3 KO compared to SS wild type rats. In addition to being mediators of inflammation, these metabolites are associated with renal cell injury and death. Furthermore, prostaglandin 6-keto-PGF 1α , which has known links to renal inflammation, was significantly (p<0.05) increased in renal cortex of SS- Pon3 KO compared to SS wild type rats. Conclusion: These findings suggest that targeted deletion of Pon3 increases pro-inflammatory eicosanoids (5-HETE and 5-HEPE) and prostaglandins (6-keto-PGF 1α ), as well as increases renal damage independent of blood pressure.

Abstract 096: Leptin and High Salt Diet Induce Greater Increases in Blood Pressure in Female than Male Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jessica L Faulkner ◽  
Eric J Belin de Chantemele
Keyword(s):  
Blood Pressure ◽  
Recovery Period ◽  
Pressure Rise ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Male And Female ◽  
Female Mice ◽  
Males And Females ◽  
Blood Pressure Responses

Recent studies by our group demonstrated that leptin is a direct regulator of aldosterone secretion and increases blood pressure via sex-specific mechanisms involving leptin-mediated activation of the aldosterone-mineralocorticoid receptor signaling pathway in females and sympatho-activation in males. Although it is well accepted that females secrete more leptin and aldosterone than males, it is unknown whether leptin infusion raises blood pressure similarly in male and female mice and whether higher aldosterone levels sensitize females to salt-induced hypertension. We hypothesized that female mice would be more sensitive to leptin than males and also have a potentiated blood pressure rise in response to high salt diet compared to males. Male and female Balb/C mice were implanted with radiotelemeters for continuous measurement of mean arterial pressure (MAP) at 10 weeks of age. MAP was measured for seven days prior to feeding with a high-salt diet (HS, 4%NaCl) for seven days. Following a recovery period, animals were then implanted with osmotic minipumps containing leptin (0.9mg/kg/day) recorded for seven days. Baseline MAP was similar between males and females (101.3±2.9 vs 99.3±3.7 mmHg, n=4 and 5, respectively), however, HS diet resulted in a greater MAP increase in females (15.0±2.6 mmHg) compared to males (3.1±4.5 mmHg, P<0.05). MAP with leptin treatment was increased with leptin in females moreso than in males, however, this did not reach significance (6.8±5.8 vs 1.8±5.9 mmHg, respectively). This potential sex difference in blood pressure responses to leptin was not associated with changes in body weight (0.07±0.44 vs -0.22±0.2 g, respectively) nor changes in blood glucose (-19.67±15.06 vs -15.4±11.4 mg/dl, respectively) in males and females in response to leptin. In summary, female mice are more sensitive to HS diet-induced blood pressure increases than males. Females may be more sensitive to leptin-mediated blood pressure increases than males. Further investigation is needed to determine whether these sex differences in blood pressure responses to HS diet and leptin are mediated by aldosterone or other mechanisms.

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.

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