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

Hypertension ◽  
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.

scholarly journals Renoprotection by statins is linked to a decrease in renal oxidative stress, TGF-β, and fibronectin with concomitant increase in nitric oxide bioavailability

2008 ◽  
Vol 295 (1) ◽  
pp. F53-F59 ◽  
Author(s):  
Ming-Sheng Zhou ◽  
Ivonne Hernandez Schuman ◽  
Edgar A. Jaimes ◽  
Leopoldo Raij
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Renal Injury ◽  
Oxidized Ldl ◽  
High Salt ◽  
Salt Diet ◽  
Enos Activity ◽  
Tgf Β1

Clinical and experimental studies have provided evidence suggesting that statins exert renoprotective effects. To investigate the mechanisms by which statins may exert renoprotection, we utilized the hypertensive Dahl salt-sensitive (DS) rat model, which manifests cardiovascular and renal injury linked to increased angiotensin II-dependent activation of NADPH oxidase and decreased nitric oxide (NO) bioavailability. DS rats given high salt diet (4% NaCl) for 10 wk exhibited hypertension [systolic blood pressure (SBP) 200 ± 8 vs. 150 ± 2 mmHg in normal salt diet (0.5% NaCl), P < 0.05], glomerulosclerosis, and proteinuria (158%). This was associated with increased renal oxidative stress demonstrated by urinary 8-F2α-isoprostane excretion and NADPH oxidase activity, increased protein expression of transforming growth factor (TGF)-β (63%) and fibronectin (181%), increased mRNA expression of the proinflammatory molecules monocyte chemoattractant protein-1 (MCP-1) and lectin-like oxidized LDL receptor-1 (LOX-1), as well as downregulation of endothelial NO synthase (eNOS) activity (−44%) and protein expression. Return to normal salt had no effect on SBP or any of the measured parameters. Atorvastatin (30 mg·kg−1·day−1) significantly attenuated proteinuria and glomerulosclerosis and normalized renal oxidative stress, TGF-β1, fibronectin, MCP-1 and LOX-1 expression, and eNOS activity and expression. Atorvastatin-treated rats showed a modest reduction in SBP that remained in the hypertensive range (174 ± 8 mmHg). Atorvastatin combined with removal of high salt normalized SBP and proteinuria. These findings suggest that statins mitigate hypertensive renal injury by restoring the balance among NO, TGF-β1, and oxidative stress and explain the added renoprotective effects observed in clinical studies using statins in addition to inhibitors of the renin-angiotensin system.

scholarly journals Studies of Salt and Stress Sensitivity on Arterial Pressure in Renin-b Deficient Mice

2021 ◽  
Author(s):  
Pablo Nakagawa ◽  
Javier Gomez ◽  
Ko-Ting Lu ◽  
Justin L. Grobe ◽  
Curt D. Sigmund
Keyword(s):  
Blood Pressure ◽  
Restraint Stress ◽  
Sodium Intake ◽  
High Salt ◽  
Ventrolateral Medulla ◽  
High Salt Diet ◽  
Blood Pressure Elevation ◽  
Salt Diet ◽  
The Brain ◽  
Deficient Mice

AbstractExcessive sodium intake is known to increase the risk for hypertension, heart disease, and stroke. Individuals who are more susceptible to the effects of high salt are at higher risk for cardiovascular diseases even independent of their blood pressure status. Local activation of the renin-angiotensin system (RAS) in the brain, among other mechanisms, has been hypothesized to play a key role in contributing to salt balance. We have previously shown that deletion of the alternative renin isoform termed renin-b disinhibits the classical renin-a encoding preprorenin in the brain resulting in elevated brain RAS activity. Thus, we hypothesized that renin-b deficiency results in higher susceptibility to salt-induced elevation in blood pressure. Telemetry implanted Ren-bNull and wildtype littermate mice were first offered a low salt diet for a week and subsequently a high salt diet for another week. A high salt diet induced a mild blood pressure elevation in both Ren-bNull and wildtype mice, but mice lacking renin-b did not exhibit an exaggerated pressor response. When renin-b deficient mice were exposed to a high salt diet for a longer duration (4 weeks), was a trend for increased myocardial enlargement in Ren-bNull mice when compared with control mice. Multiple studies have also demonstrated the association of chronic and acute environmental stress with hypertension. Activation of the RAS in the rostral ventrolateral medulla and the hypothalamus is required for stress-induced hypertension. Thus, we next questioned whether the lack of renin-b would result in exacerbated response to an acute restraint-stress. Wildtype and Ren-bNull mice equally exhibited elevated blood pressure in response to restraint-stress, which was similar in mice fed either a low or high salt diet. These studies highlight a complex mechanism that masks/unmasks roles for renin-b in cardiovascular physiology.

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

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.

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.

scholarly journals Regulation of blood pressure, oxidative stress and AT1R by high salt diet in mutant human dopamine D5 receptor transgenic mice

2015 ◽  
Vol 38 (6) ◽  
pp. 394-399 ◽  
Author(s):  
Xing Liu ◽  
Wenjie Wang ◽  
Wei Chen ◽  
Xiaoliang Jiang ◽  
Yanrong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Transgenic Mice ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dopamine D5 Receptor ◽  
Regulation Of Blood Pressure

scholarly journals Transgenic Mice Overexpressing Human Alpha-1 Antitrypsin Exhibit Low Blood Pressure and Altered Epithelial Transport Mechanisms in the Inactive and Active Cycles

2021 ◽  
Vol 12 ◽  
Author(s):  
Lauren P. Liu ◽  
Mohammed F. Gholam ◽  
Ahmed Samir Elshikha ◽  
Tamim Kawakibi ◽  
Nasseem Elmoujahid ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Natriuretic Peptide ◽  
Cathepsin B ◽  
High Salt ◽  
Kidney Cortex ◽  
Wild Type ◽  
High Salt Diet ◽  
Salt Diet ◽  
Alpha 1 Antitrypsin

Human alpha-1 antitrypsin (hAAT) is a versatile protease inhibitor, but little is known about its targets in the aldosterone-sensitive distal nephron and its role in electrolyte balance and blood pressure control. We analyzed urinary electrolytes, osmolality, and blood pressure from hAAT transgenic (hAAT-Tg) mice and C57B/6 wild-type control mice maintained on either a normal salt or high salt diet. Urinary sodium, potassium, and chloride concentrations as well as urinary osmolality were lower in hAAT-Tg mice maintained on a high salt diet during both the active and inactive cycles. hAAT-Tg mice showed a lower systolic blood pressure compared to C57B6 mice when maintained on a normal salt diet but this was not observed when they were maintained on a high salt diet. Cathepsin B protein activity was less in hAAT-Tg mice compared to wild-type controls. Protein expression of the alpha subunit of the sodium epithelial channel (ENaC) alpha was also reduced in the hAAT-Tg mice. Natriuretic peptide receptor C (NPRC) protein expression in membrane fractions of the kidney cortex was reduced while circulating levels of atrial natriuretic peptide (ANP) were greater in hAAT-Tg mice compared to wild-type controls. This study characterizes the electrolyte and blood pressure phenotype of hAAT-Tg mice during the inactive and active cycles and investigates the mechanism by which ENaC activation is inhibited in part by a mechanism involving decreased cathepsin B activity and increased ANP levels in the systemic circulation.

scholarly journals Studies of salt and stress sensitivity on arterial pressure in renin-b deficient mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0250807
Author(s):  
Pablo Nakagawa ◽  
Javier Gomez ◽  
Ko-Ting Lu ◽  
Justin L. Grobe ◽  
Curt D. Sigmund
Keyword(s):  
Blood Pressure ◽  
Restraint Stress ◽  
Statistical Significance ◽  
High Salt ◽  
Ventrolateral Medulla ◽  
High Salt Diet ◽  
Blood Pressure Elevation ◽  
Salt Diet ◽  
The Brain ◽  
Deficient Mice

Excessive sodium intake is known to increase the risk for hypertension, heart disease, and stroke. Individuals who are more susceptible to the effects of high salt are at higher risk for cardiovascular diseases even independent of their blood pressure status. Local activation of the renin-angiotensin system (RAS) in the brain, among other mechanisms, has been hypothesized to play a key role in contributing to salt balance. We have previously shown that deletion of the alternative renin isoform termed renin-b disinhibits the classical renin-a encoding preprorenin in the brain resulting in elevated brain RAS activity. Thus, we hypothesized that renin-b deficiency results in higher susceptibility to salt-induced elevation in blood pressure. Telemetry implanted Ren-bNull and wildtype littermate mice were first offered a low salt diet for a week and subsequently a high salt diet for another week. A high salt diet induced a mild blood pressure elevation in both Ren-bNull and wildtype mice, but mice lacking renin-b did not exhibit an exaggerated pressor response. When renin-b deficient mice were exposed to a high salt diet for a longer duration (4 weeks), there was a trend for increased myocardial enlargement in Ren-bNull mice when compared with control mice, but this did not reach statistical significance. Multiple studies have also demonstrated the association of environmental stress with hypertension. Activation of the RAS in the rostral ventrolateral medulla and the hypothalamus is required for stress-induced hypertension. Thus, we next questioned whether the lack of renin-b would result in exacerbated response to an acute restraint-stress. Wildtype and Ren-bNull mice equally exhibited elevated blood pressure in response to restraint-stress, which was similar in mice fed either a low or high salt diet. These studies suggest that mechanisms unrelated to salt and acute stress alter the cardiovascular phenotype in mice lacking renin-b.

scholarly journals THE EFFECTS OF HIGH SALT DIET AND EXERCISE ON THE WATER-SALT BALANCE AND BLOOD PRESSURE IN RATS

2021 ◽  
pp. 47-54
Author(s):  
Buket GÜNGÖR ◽  
Afet Seçil AKDUR ◽  
Coskun SILAN ◽  
Hakki Engin AKSULU ◽  
Orhan ŞAHİN
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Vascular Tissue ◽  
High Salt ◽  
Dopamine Synthesis ◽  
Salt Balance ◽  
High Salt Diet ◽  
Salt Diet ◽  
Intensive Exercise ◽  
Water Salt

In the study which was prepared based on the factors that can take place in essential hypertension pathology; We aimed to investigate the interactions of intensive exercise, high salt and partial NOS inhibition applications with each other, the effects on water-salt balance and blood pressure, changes in the intrarenal dopaminergic system, which is an important natriuretic system, and the participation of oxidative stress. The rats were given intensive exercise on a treadmill at a speed of 25 m / min at 5% inclination for 30 minutes a day, LNNA at a concentration of 50 mg / L and a high salt diet of 4% for 7 days either separately or together. Blood pressures of the rats were measured on the first and last days of the experiment, and the rats were taken into metabolic cages; 24-hour water intake and urinevolume were measured. Dopamine levels were measured in 24-hour urine to detect intrarenal dopamine synthesis. In addition, oxidative stress parameters in the serums of rats; TAS, TOS and OSI levels were measured. Blood pressure was found to be high in the groups in which intensive exercise was applied together with LNNA and high salt diet. While there was no change in the water balance of this group, it was found that sodium excretion and dopamine levels increased in 24-hour urine. In addition, it was found that the total oxidant status increased in this group, and oxidative stress developed as a result of insufficient antioxidant system. It suggests that the reason of hypertension that develops with the application of intensive exercise together with LNNA and high salt diet may be due to the vascular resistance increasing effect of oxidative stress rather than water-salt retention and it points out the necessity of studies to fully detect vascular tissue oxidative stress markers and vascular oxidative damage.

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

2020 ◽  
Vol 13 (4) ◽  
pp. 695-705
Author(s):  
Olayinka Christianah Jayeola ◽  
Ademola Adetokunbo Oyagbemi ◽  
Omolara Ibiwunmi Okunlola ◽  
Olayiwola Olubamiwa ◽  
Temidayo Olutayo Omobowale ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Antioxidant Status ◽  
Renal Damage ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Cocoa Powder ◽  
Markers Of Inflammation

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.

Sign in / Sign up

Export Citation Format

Share Document