Effect of cocoa powder on hypertension and antioxidant status in uninephrectomized hypertensive rats

Background and Aim: High salt diet and uninephrectomy are associated with high blood pressure with attendant cardiovascular disease conditions such as hypertension, renal damage, myocardial infarction, and stroke. The aim of this study was to investigate the beneficial effects of consumption of cocoa and cocoa-containing products in the management of high blood pressure in uninephrectomized hypertensive rats. Materials and Methods: The effect of cocoa powder on blood pressure, markers of inflammation, oxidative stress, and histopathology were investigated in uninephrectomized animals fed with cocoa feed alone or in combination with a high salt diet. Male rats were randomly divided into five groups: Group A was the control group and fed with normal feed alone, Group B was fed with cocoa feed alone, Group C was fed with high salt diet (8% salt), Group D was fed with cocoa-feed compounded with 8% salt for 4 weeks after uninephrectomy, and Group E was uninephrectomized rats on a normal diet. The left kidneys of animals in Groups C, D, and E were removed by surgery. After 4 weeks of treatment, the systolic, diastolic, and mean arterial blood pressure was measured. The serum markers of renal damage and oxidative stress were determined. Histological examination was also performed on renal and cardiac tissues. Results: Results showed significant increases in biomarkers of oxidative stress, inflammation, and renal damage with a concomitant decrease in antioxidant status in hypertensive uninephrectomized rats. Cocoa feed, however, significantly improved blood pressure and nitric oxide bioavailability, antioxidant status and reduced markers of inflammation and oxidative stress. Conclusion: These findings show that cocoa powder could be used to maintain blood pressure levels in hypertensive rats through its antioxidant capacity.

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Abstract 370: Upregulation of Renal D5 Dopamine Receptor Ameliorates Hypertension in D3 Deficient Mice

Hypertension ◽

10.1161/hyp.60.suppl_1.a370 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Xiaoyan Wang ◽

Crisanto S Escano ◽

Laureano Asico ◽

John E Jones ◽

Alan Barte ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Nadph Oxidase ◽

Protein Expression ◽

Dopamine Receptors ◽

Dopamine Receptor ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Deficient Mice

D 3 dopamine receptor (D 3 R) deficient mice have renin-dependent hypertension but the hypertension is mild and is not associated with oxidative stress. In order to determine if any compensatory mechanism in the kidney is involved in the regulation of blood pressure with disruption of D 3 R, we measured the renal protein expression of dopamine receptors in D 3 R homozygous (D 3 -/-) and heterozygous (D 3 +/-) knockout mice and their wild type (D 3 +/+) littermates. D 5 dopamine receptor (D 5 R) (169±23%, reported as % of D 3 +/+, n=5/group) expression was increased but D 4 dopamine receptors protein expression (59±8%) was decreased, while no significant changes were found with D 1 and D 2 dopamine receptors. Immunocytochemistry showed a stronger renal staining of D 5 R but without a change in renal tubule cell distribution in D 3 -/- relative to D 3 +/+ mice. D 5 R abundance was also increased in D 3 +/- (205±30%, n=5/group) relative to D 3 +/+ mice, while D 1 R abundance was similar between D 3 +/- and D 3 +/+ mice. The increase in D 5 R expression was abolished while blood pressure was increased further in D 3 -/- mice fed a high salt diet. Treatment of the D 1 -like (including D 1 and D 5 receptors) antagonist, SCH23390 , increased the blood pressure to a greater extent in anesthetized D 3 -/- mice than in D 3 +/+ mice (n=4/group), suggesting that the upregulation of D 5 R may modulate the hypertension in mice caused by the disruption of D 3 R. Since dopamine inhibits the NADPH oxidase-induced production of reactive oxygen species (ROS) via the D 5 R, we also measured the protein expression of NOXs in the kidney and isoprostane in the urine. No NADPH oxidase subunit was increased in D 3 -/- and D 3 +/- mice relative to D 3 +/+ mice fed a normal or salt high salt diet, and urinary isoprostane excretion was also similar in D 3 -/- and D 3 +/+ mice. Our findings suggest that the upregulation of D 5 R may minimize the hypertension and prevent oxidative stress in D 3 -/- mice.

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Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms21062248 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2248 ◽

Cited By ~ 1

Author(s):

Abu Sufiun ◽

Asadur Rahman ◽

Kazi Rafiq ◽

Yoshihide Fujisawa ◽

Daisuke Nakano ◽

...

Keyword(s):

Blood Pressure ◽

Circadian Rhythm ◽

Renal Injury ◽

Tissue Injury ◽

Renal Tissue ◽

High Salt ◽

Hypertensive Rats ◽

High Salt Diet ◽

Salt Diet ◽

The Difference

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension.

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Alamandine alleviates hypertension and renal damage via oxidative-stress attenuation in Dahl rats

Cell Death Discovery ◽

10.1038/s41420-022-00822-y ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Juexiao Gong ◽

Man Luo ◽

Yonghong Yong ◽

Shan Zhong ◽

Peng Li

Keyword(s):

Oxidative Stress ◽

Renal Dysfunction ◽

Renal Damage ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Renal Tubular Cells ◽

Induced Hypertension

AbstractAlamandine (Ala) is a novel member of the renin–angiotensin-system (RAS) family. The present study aimed to explore the effects of Ala on hypertension and renal damage of Dahl salt-sensitive (SS) rats high-salt diet-induced, and the mechanisms of Ala on renal-damage alleviation. Dahl rats were fed with high-salt diets to induce hypertension and renal damage in vivo, and HK-2 cells were treated with sodium chloride (NaCl) to induce renal injury in vitro. Ala administration alleviated the high-salt diet-induced hypertension, renal dysfunction, and renal fibrosis and apoptosis in Dahl SS rats. The HK-2 cells’ damage, and the increases in the levels of cleaved (c)-caspase3, c-caspase8, and c-poly(ADP-ribose) polymerase (PARP) induced by NaCl were inhibited by Ala. Ala attenuated the NaCl-induced oxidative stress in the kidney and HK-2 cells. DETC, an inhibitor of SOD, reversed the inhibitory effect of Ala on the apoptosis of HK-2 cells induced by NaCl. The NaCl-induced increase in the PKC level was suppressed by Ala in HK-2 cells. Notably, PKC overexpression reversed the moderating effects of Ala on the NaCl-induced apoptosis of HK-2 cells. These results show that Ala alleviates high-salt diet-induced hypertension and renal dysfunction. Ala attenuates the renal damage via inhibiting the PKC/reactive oxygen species (ROS) signaling pathway, thereby suppressing the apoptosis in renal tubular cells.

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High salts intake, cardiovascular system and kidney in spontaneous hypertensive rats

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2017-16-3-62-69 ◽

2017 ◽

Vol 16 (3) ◽

pp. 62-69

Author(s):

A. G. Kucher ◽

O. N. Beresneva ◽

M. M. Parastaeva ◽

G. T. Ivanova ◽

M. I. Zarajsky ◽

...

Keyword(s):

Gene Expression ◽

Blood Pressure ◽

Heart Rate ◽

Cardiovascular System ◽

High Salt ◽

Myocardial Remodeling ◽

Hypertensive Rats ◽

Relative Level ◽

High Salt Diet ◽

Salt Diet

Objective. To study the influence of diet containing high or normal NaCl on the arterial blood pressure level (BP), heart rate (HR), processes of myocardial remodeling and of nuclear transcription factor kB (NFkB) expression in myocardium and kidney in spontaneously hypertensive rats (SHR). Design and methods. The two groups of male SHRs received a diet with normal (0.34 %; n = 24, control) and high content of NaCl (8.0 %; n = 25; experimental group) for 2 months. Blood pressure (BP), heart rate (HR), cardiac left ventricular mass index (LVMI), left (LKMI) and right (RKMI) kidney mass indexes were determined. Morphological study of myocardium (light microscopy), including quantitative morphometry was carried out. In part of animals the relative level of NFkB gene expression in heart and kidney tissues was studied. Results and discussion. In rats fed a diet containing 8 % NaCl BP and HR did not change significantly compared with the control. However, LVMI, RKMI, LKMI were significantly higher in high-salt diet-treated animals than in controls. The heart of high-salt diet-treated animals developed the changes leading to hypertrophy and possibly hyperplasia of cardiomyocytes. In these animals, perivascular fibrosis, significant increase of arterial wall thickness and vacuolization of smooth muscle cells were revealed. The relative level of NFKB gene expression in rats receiving high-salt diet was 33-fold higher in myocardium and 12-fold higher in kidneys than in animals fed a normal salt diet. Conclusion. The high-salt diet is not necessarily accompanied by an increase in blood pressure, but causes myocardial remodeling, apparently due to direct «toxic» effects. The negative impact on the cardiovascular system of high-salt diet is in part mediated through NFkB-associated signaling pathways. Furthermore, high NaCl diet causes activation of NFkB in the kidneys.

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Multiple blood pressure loci on rat chromosome 13 attenuate development of hypertension in the Dahl S hypertensive rat

Physiological Genomics ◽

10.1152/physiolgenomics.00280.2006 ◽

2007 ◽

Vol 31 (2) ◽

pp. 228-235 ◽

Cited By ~ 59

Author(s):

Carol Moreno ◽

Mary L. Kaldunski ◽

Tao Wang ◽

Richard J. Roman ◽

Andrew S. Greene ◽

...

Keyword(s):

Blood Pressure ◽

Renal Damage ◽

High Salt ◽

Male Rats ◽

Brown Norway ◽

High Salt Diet ◽

Salt Diet ◽

Chromosome 13 ◽

Congenic Strains ◽

Multiple Blood

Previous studies have indicated that substitution of chromosome 13 of the salt-resistant Brown Norway BN/SsNHsdMcwi (BN) rat into the genomic background of the Dahl salt-sensitive SS/JrHsdMcwi (SS) rat attenuates the development of salt-sensitive hypertension and renal damage. To identify the regions within chromosome 13 that attenuate the development of hypertension during a high-salt diet in the SS rat, we phenotyped a series of overlapping congenic lines covering chromosome 13, generated from an intercross between the consomic SS-13BN rat and the SS rat. Blood pressure was determined in chronically catheterized rats after 2 wk of high-salt diet (8% NaCl) together with microalbuminuria as an index of renal damage. Four discrete regions were identified, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from hypertension during high-salt diet, reducing blood pressure by 20–29 mmHg. Protection was more robust in female than male rats in some of the congenic strains, suggesting a sex interaction with some of the genes determining blood pressure during high-salt diet. Among the 23 congenic strains, several regions overlapped. When three of the “protective” regions were combined onto one broad congenic strain, no summation effect was seen, obtaining the same decrease in blood pressure as with each one independently. We conclude from these studies that there are four regions within chromosome 13 containing genes that interact epistatically and influence arterial pressure.

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High-salt diet upregulates kininogen and downregulates tissue kallikrein expression in Dahl-SS and SHR rats

AJP Renal Physiology ◽

10.1152/ajprenal.1996.271.4.f824 ◽

1996 ◽

Vol 271 (4) ◽

pp. F824-F830 ◽

Cited By ~ 5

Author(s):

C. Wang ◽

C. Chao ◽

L. M. Chen ◽

L. Chao ◽

J. Chao

Keyword(s):

Blood Pressure ◽

High Salt ◽

Transcriptional Level ◽

Tissue Kallikrein ◽

Mrna Levels ◽

Hypertensive Rats ◽

High Salt Diet ◽

Salt Loading ◽

Salt Diet ◽

Sd Rats

Tissue kallikrein cleaves low-molecular-weight (low-M(r)) kininogen to produce the vasoactive kinin peptide. It has been suggested that hypertensive patients with low urinary kallikrein excretion may have a defect in sodium handling. In this study, we examined the effect of a high-salt diet on the expression of tissue kallikrein and kininogen genes in Dahl salt-sensitive rats (Dahl-SS), spontaneously hypertensive rats (SHR), and normotensive Sprague-Dawley rats (SD) by Northern and Western blot analysis and radioimmunoassay. Control and experimental groups received normal and high-salt diets containing 0.4% and 8% NaCl, respectively, for 6 wk. High-salt diet induced a significant time-dependent increase of blood pressure in both strains of hypertensive rats and a slight but significant increase of blood pressure in normotensive SD rats. Hepatic kininogen mRNA levels of both Dahl-SS and SHR on a high-salt diet increased 2.4-fold and 2.0-fold, respectively, while alpha 1-antitrypsin mRNA levels were not changed in rats receiving high-salt diet. Immunoreactive total kininogen and low-M(r) kininogen (58 kDa) levels in sera increased in response to high-salt diet in both strains of hypertensive rats. In SD rats, the low-M(r) kininogen level in sera was unaltered, whereas total kininogen increased in response to high-salt diet. Tissue kallikrein mRNAs in the kidney and salivary glands of Dahl-SS, SHR, and SD rats were reduced, whereas beta-actin mRNA was not altered by high-salt diet. Similarly, immunoreactive intrarenal kallikrein levels were reduced in these rats in response to high-salt diet. These studies show that increases in blood pressure after salt loading in Dahl-SS and SHR are accompanied by increases in low-M(r) kininogen. Tissue kallikrein gene expression in hypertensive Dahl-SS and SHR and normotensive SD rats is suppressed after salt loading. These findings show that reduced renal kallikrein expression and increased kininogen expression is regulated at the transcriptional level during salt loading.

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Endothelin ETBreceptors contribute to sex differences in blood pressure elevation in angiotensin II hypertensive rats on a high-salt diet

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.12084 ◽

2013 ◽

Vol 40 (6) ◽

pp. 362-370 ◽

Cited By ~ 28

Author(s):

Wararat Kittikulsuth ◽

Stephen W Looney ◽

David M Pollock

Keyword(s):

Blood Pressure ◽

Sex Differences ◽

Angiotensin Ii ◽

High Salt ◽

Hypertensive Rats ◽

High Salt Diet ◽

Blood Pressure Elevation ◽

Salt Diet ◽

Pressure Elevation

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Bilateral Paraventricular Nucleus Upregulation of Extracellular Superoxide Dismutase Decreases Blood Pressure by Regulation of the NLRP3 and Neurotransmitters in Salt-Induced Hypertensive Rats

Frontiers in Pharmacology ◽

10.3389/fphar.2021.756671 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qing Su ◽

Xiao-Jing Yu ◽

Xiao-Min Wang ◽

Hong-Bao Li ◽

Ying Li ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Salt Intake ◽

High Salt ◽

Extracellular Superoxide Dismutase ◽

Ros Production ◽

Gaba Level ◽

Sod Activity ◽

High Salt Diet ◽

Salt Diet

Aims: Long-term salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular superoxide dismutase (Ec-SOD) is a unique antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive reactive oxygen species (ROS). However, the underlying mechanism of Ec-SOD in the PVN remains unclear.Methods: Sprague–Dawley rats (150–200 g) were fed either a high salt diet (8% NaCl, HS) or normal salt diet (0.9% NaCl, NS) for 6 weeks. Each group of rats was administered with bilateral PVN microinjection of AAV-Ec-SOD (Ec-SOD overexpression) or AAV-Ctrl for the next 6 weeks.Results: High salt intake not only increased mean arterial blood pressure (MAP) and the plasma noradrenaline (NE) but also elevated the NAD(P)H oxidase activity, the NAD(P)H oxidase components (NOX2 and NOX4) expression, and ROS production in the PVN. Meanwhile, the NOD-like receptor protein 3 (NLRP3)–dependent inflammatory proteins (ASC, pro-cas-1, IL-β, CXCR, CCL2) expression and the tyrosine hydroxylase (TH) expression in the PVN with high salt diet were higher, but the GSH level, Ec-SOD activity, GAD67 expression, and GABA level were lower than the NS group. Bilateral PVN microinjection of AAV-Ec-SOD decreased MAP and the plasma NE, reduced NAD(P)H oxidase activity, the NOX2 and NOX4 expression, and ROS production, attenuated NLRP3-dependent inflammatory expression and TH, but increased GSH level, Ec-SOD activity, GAD67 expression, and GABA level in the PVN compared with the high salt group.Conclusion: Excessive salt intake not only activates oxidative stress but also induces the NLRP3-depensent inflammation and breaks the balance between inhibitory and excitability neurotransmitters in the PVN. Ec-SOD, as an essential anti-oxidative enzyme, eliminates the ROS in the PVN and decreases the blood pressure, probably through inhibiting the NLRP3-dependent inflammation and improving the excitatory neurotransmitter release in the PVN in the salt-induced hypertension.

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Exercise Training Attenuates Proinflammatory Cytokines, Oxidative Stress and Modulates Neurotransmitters in the Rostral Ventrolateral Medulla of Salt-Induced Hypertensive Rats

Cellular Physiology and Biochemistry ◽

10.1159/000492095 ◽

2018 ◽

Vol 48 (3) ◽

pp. 1369-1381 ◽

Cited By ~ 7

Author(s):

Hong-Bao Li ◽

Chan-Juan Huo ◽

Qing Su ◽

Xiang Li ◽

Juan Bai ◽

...

Keyword(s):

Oxidative Stress ◽

Exercise Training ◽

Sympathetic Nerve Activity ◽

High Salt ◽

Ventrolateral Medulla ◽

Gamma Aminobutyric Acid ◽

Hypertensive Rats ◽

Nerve Activity ◽

High Salt Diet ◽

Salt Diet

Background/Aims: Exercise training (ExT) was associated with cardiovascular diseases including hypertension. The rostral ventrolateral medulla (RVLM) is a key region for central control of blood pressure and sympathetic nerve activity. Therefore, this study aimed to investigate the mechanisms within RVLM that can influence exercise training induced effects in salt-induced hypertension. Methods: Male Wistar rats were fed with a normal salt (0.3%) (NS) or a high salt (8%) (HS) diet for 12 weeks to induce hypertension. Then these rats were given moderate-intensity ExT for a period of 12 weeks. RVLM was used to determine glutamate and gamma-aminobutyric acid (HPLC), phosphorylated IKKβ, Fra-LI, 67-kDa isoform of glutamate decarboxylase (GAD67), proinflammatory cytokines (PIC) and NADPH-oxidase (NOX) subunits expression (Immunohistochemistry and Immunofluorescence, Western blotting). PIC and NF-κB p65 activity in the plasma were evaluated by ELISA studies. Renal sympathetic nerve activity (RSNA) was recorded and analyzed using the PowerLab system. Results: High salt diet resulted in increased mean arterial pressure and cardiac hypertrophy. These high salt diet rats had higher RVLM levels of glutamate, PIC, phosphorylated IKKβ, NF-κB p65 activity, Fra-LI, superoxide, NOX-2 (gp91phox) and 4, and lower RVLM levels of gamma-aminobutyric acid and GAD67, and higher plasma levels of PIC, norepinephrine, and higher RSNA. ExT attenuated these changes in salt-induced hypertensive rats. Conclusions: These findings suggest that high salt diet increases the activity of NF-κB and the levels of PIC and oxidative stress, and induces an imbalance between excitatory and inhibitory neurotransmitters in the RVLM. ExT attenuates hypertension and cardiac hypertrophy partially mediated by attenuating oxidative stress and modulating neurotransmitters in the RVLM.

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