High‐salt diet promotes crystal deposition through hypertension in Dahl salt‐sensitive rat model

Abstract Preeclampsia is a common medical condition during pregnancy and a major cause of maternal and prenatal mortality. The present study was conducted to investigate the effects of maternal treatment with pentaerythritol tetranitrate (PETN) in Dahl salt-sensitive rats (DSSR), a model of superimposed preeclampsia. F0 parental DSSR were treated with PETN (50 mg/kg) from the time point of mating to the end of lactation. Maternal PETN treatment improved fetal growth and had no effect on blood pressure in DSSR offspring fed with normal chow or high-salt diet. Upon high-fat diet (HFD) feeding, offspring from PETN-treated mother showed improved glucose tolerance despite similar weight gain. Unexpectedly, maternal PETN treatment significantly potentiated the HFD-induced blood pressure elevation in male DSSR offspring. Endothelium-derived hyperpolarization factor (EDHF)-mediated vasodilation was similar between NCD-fed and HFD-fed control offspring but was markedly reduced in HFD-fed PETN offspring. EDHF genes were downregulated in the vasculature of HFD-fed PETN offspring, which was associated with epigenetic changes in histone modifications. In conclusion, maternal PETN treatment in DSSR shows both beneficial and unfavorable effects. It improves fetal growth and ameliorates glucose tolerance in the offspring. Although maternal PETN treatment has no effect on blood pressure in offspring fed with normal chow or high-salt diet, the offspring is at higher risk to develop HFD-induced hypertension. PETN may potentiate the blood pressure response to HFD by epigenetic modifications of EDHF genes. Key messages The core findings of this article suggest that maternal PETN treatment of DSSR, a rat model of a spontaneous superimposed preeclampsia, leads to • Improvement of fetal growth; • No changes of maternal blood pressure or markers of preeclampsia; • Amelioration of HFD-induced glucose intolerance in adult offspring; • No changes in blood pressure development of the offspring on normal chow or high salt-diet; • Potentiation of blood pressure elevation of the offspring on HFD.

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Abstract 500: The Cardiorenal Effects Of An Angiotensin Receptor Blocker (Valsartan) And Neprilysin Inhibitor (AHU377) Co-administered Daily For 6 Weeks In The Dahl Salt-sensitive Rat Model Of Volume-dependent Hypertension

Hypertension ◽

10.1161/hyp.64.suppl_1.500 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Alexander J McNamara ◽

Laxminarayan G Hegde ◽

Uwe Klein ◽

Craig Hill ◽

Cecile Yu ◽

...

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Weight Gain ◽

Rat Model ◽

Renal Injury ◽

Body Weight Gain ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Neprilysin Inhibitor

The endogenous natriuretic peptide system helps maintain cardiovascular homeostasis by counterbalancing the deleterious effects of renin angiotensin system activation. This study examined whether the co-administration of an ARB (valsartan: VAL) with a NEPi (AHU377: AHU) can reduce cardiorenal disease progression in the Dahl salt-sensitive (Dahl/SS) rat model of volume-dependent hypertension. Methods: Studies were conducted in conscious Dahl/SS hypertensive rats that were maintained on a high salt diet and surgically implanted with telemetry transmitters for monitoring blood pressure. Rats were treated for 6 weeks with either vehicle, VAL (30 mg/kg, PO) or VAL+AHU (30 + 30 mg/kg, PO). Changes in cardiac and renal functions were measured via Left Ventricle (LV) pressure-volume loops and biomarkers (KIM-1, NGAL and osteopontin). Results: Dahl/SS rats maintained on a high salt diet exhibited a progressive decrease in body weight gain, progressive increases in blood pressure and elevation of plasma and urinary biomarkers indicative of cardiac stress or renal injury. VAL and VAL+AHU both improved body weight gain and blunted the progressive hypertension. However, the magnitude of the antihypertensive effect was greater for VAL+AHU (peak change: - 33 ± 3 mmHg) than for VAL alone (peak change: -15 ± 5 mmHg). VAL+AHU treatment provided greater renal protective effects, based on renal biomarkers KIM-1 (286 ± 29 vs. 341 ± 59 ng), NGAL (58 ±9 vs. 108 ± 28 μg) and osteopontin (1637 ± 372 vs 2155 ± 748 ng), than VAL alone. The VAL+AHU treatment group demonstrated a greater normalization in LV function, with improved systolic contractility over VAL alone (preload-adjusted PWR max = 1 ± 0.1 vs. 2 ± 0.5 μWatt/uL). Most notably, the VAL+AHU group exhibited a greater survival rate (94%: 15 of 16) than either the VAL (75%: 12 of 16) or vehicle (70%: 14 of 20) groups. Conclusion: In summary, chronic co-administration of an ARB and NEPi to Dahl/SS rats significantly attenuated progression of hypertension, suppressed increases in biomarkers indicative of renal injury, improved cardiac function and increased overall survival. These results suggest that co-administration of an ARB and NEPi may confer a beneficial therapeutic strategy for the treatment of cardiorenal disease.

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The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure

Scientific Reports ◽

10.1038/srep39752 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 15

Author(s):

Tomohiko Ono ◽

Naomi Kamimura ◽

Tomohiro Matsuhashi ◽

Toshihiro Nagai ◽

Takahiko Nishiyama ◽

...

Keyword(s):

Heart Failure ◽

Rat Model ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Histone 3

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The metabolic profile of a rat model of chronic kidney disease

PeerJ ◽

10.7717/peerj.3352 ◽

2017 ◽

Vol 5 ◽

pp. e3352 ◽

Cited By ~ 7

Author(s):

Yohei Tanada ◽

Junji Okuda ◽

Takao Kato ◽

Eri Minamino-Muta ◽

Ichijiro Murata ◽

...

Keyword(s):

Gene Expression ◽

Chronic Kidney Disease ◽

Energy Metabolism ◽

Kidney Disease ◽

Rat Model ◽

Elevated Serum ◽

High Salt ◽

Suitable Model ◽

High Salt Diet ◽

Salt Diet

BackgroundThe kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension.MethodsWe used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney.ResultsDS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased.ConclusionsDS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

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Implantation and pregnancy outcome of rats fed with low and high salt diet

Endocrine Abstracts ◽

10.1530/endoabs.38.p361 ◽

2015 ◽

Author(s):

Iranloye Bolanle ◽

Oludare Gabriel

Keyword(s):

Pregnancy Outcome ◽

High Salt ◽

High Salt Diet ◽

Salt Diet

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463-P: Deterioration of Atherosclerosis via Dysbiosis in ApoE Null Mice Fed with High-Salt Diet

Diabetes ◽

10.2337/db20-463-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 463-P

Author(s):

TOMONORI KIMURA ◽

YOSHITAKA HASHIMOTO ◽

TAKAFUMI SENMARU ◽

EMI USHIGOME ◽

MASAHIDE HAMAGUCHI ◽

...

Keyword(s):

High Salt ◽

High Salt Diet ◽

Salt Diet

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Faculty Opinions recommendation of ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718876812.793503540 ◽

2015 ◽

Author(s):

Fredrik Palm

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

High Salt ◽

Oxygen Species ◽

High Salt Diet ◽

Salt Diet

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

International Journal of Molecular Sciences ◽

10.3390/ijms20143495 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3495 ◽

Cited By ~ 1

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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