Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

Berger, Rebeca Caldeira Machado; Vassallo, Paula Frizera; Crajoinas, Renato Oliveira; Oliveira, Marilene; Martins, Flavia L; Nogueira, Breno Valentim; Motta‐Santos, Daisy; Araújo, Isabella Binotti; Forechi, Ludimila; Girardi, Adriana C. C.; Santos, Robson Augusto Souza; Mill, José Geraldo

doi:10.1371/journal.pone.0141288

Cited by 30 publications

(27 citation statements)

References 52 publications

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“…Additionally, antioxidant treatment with tempol reversed the imbalance of renal RAS components and led to diuresis and natriuresis, lowering obesity-related hypertension. Furthermore, a high salt diet in SHR produced glomerular hypertrophy and decreased ACE2 and nephrin expressions[52]. …”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet

Cao¹,

Penna²,

Kouyoumdzian³

et al. 2017

WJN

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AIMTo determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system.METHODSSprague-Dawley rats were fed with 8% NaCl high-salt (HS) or 0.4% NaCl (normal-salt, NS) diet for 3 wk, with or without tempol (T) (1 mmol/L, administered in drinking water). Mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa) were measured. We evaluated angiotensin II (Ang II), angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), mas receptor (MasR), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) in renal tissues by immunohistochemistry.RESULTSThe intake of high sodium produced a slight but significant increase in MAP and differentially regulated components of the renal renin-angiotensin system (RAS). This included an increase in Ang II and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang II and AT1R, as increase in AT2, ACE2, Ang (1-7) and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang (1-7) and MasR.CONCLUSIONThese findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang II. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet

Cao¹,

Penna²,

Kouyoumdzian³

et al. 2017

WJN

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“…Rats were placed in individual metabolic cages (Tecniplast 304) during 48 h for analysis of food and water consumption as previous published by Berger et al [21]. The first 24 h were used for adaptation and the following 24 h were used to record food and water intake.…”

Section: Methodsmentioning

confidence: 99%

Effects of controlled doses of Oxyelite Pro on physical performance in rats

et al. 2016

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BackgroundOxyElite Pro (OEP) is a dietary supplement to increase metabolism which contains as key stimulant the ingredient 1,3-dimethylamylamine (DMAA). Serious adverse effects have been reported after OEP consumption however, these effects are related to poisoning or overdose. To our knowledge, no one studied the effects of OEP at controlled doses. Thus, the aim of this study was to evaluate acute and chronic OEP affects, at controlled doses in Wistar rats, on physical performance, metabolic parameters, liver injury markers and oxidative stress markers and mitochondrial biogenesis in skeletal muscle.MethodsRats were divided in control, 4.3 mg OEP/kg, 12.9 mg OEP/kg and 25.8 mg OEP/kg. All groups were submitted to supplementation with OEP for 4 weeks and the experimental protocols were performed 30 min after the first OEP administration (acute response) and 30 min after the last OEP administration at the end of the forth week (chronic response).ResultsRunning distance and running time increased after acute administration of 12.9 mg OEP/kg (2.6-fold) and 25.8 mg OEP/kg (2.8-fold). Since no effect on the exercise tolerance test was observed at the lower OEP dose (4.3 mg OEP/kg), this group was removed from further analyzes. On other hand, running distance and running time decreased after daily supplementation for 4 weeks also in both groups (64% in 12.9 mg OEP/kg and 72% in 25.8 mg OEP/kg). Chronic supplementation at both 12.9 and 25.8 mg OEP/kg decreased TBARS levels in soleus muscle (36 and 31%) and liver (43 and 25%). AOPP was also decreased by both doses in the liver (39 and 45%). Chronic administration of the highest dose, 25.8 mg OEP/kg, was able to reduce mRNA expression of PGC-1α in soleus muscle (25%). No effect was found in other analyses such as spontaneous physical activity, body weight, food and water intake, hepatic toxicity, cardiac oxidative stress and mitochondrial DNA amount.ConclusionMaximum and not recommended doses of OEP ingested acutely presented stimulating effect on the ability to exercise. However, its daily consumption for 4 weeks showed antioxidant effects in soleus muscle and liver which may have decreased the PGC-1α mRNA expression on soleus muscle and contributed to the impaired performance in the exercise tolerance test.

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“…In the kidney specifically, ACE2 is highly expressed in tubular and glomerular epithelium, vascular smooth muscle cells, the endothelium of interlobular arteries, and glomerular mesangial cells [23, 26]. Similar to ACE, expression of ACE2 is altered in many renal disease states such as diabetic nephropathy [27•, 28•], hypertensive renal disease [29•, 30], Alport syndrome [31, 32], and renal fibrosis [33•, 34•]. …”

Section: Ace and Acementioning

confidence: 99%

“…It has generally been understood that the ACE2/Ang(1–7)/Mas axis acts to counterregulate the vasoconstrictive and hypertensive activity of the ACE/Ang II/AT1R axis. Recent studies showed that high-salt diet in spontaneously hypertensive rats decreased ACE2 expression while increasing the ACE/ACE2 ratio, glomerular hypertrophy, loss of the podocytes foot processes, and proteinuria [29•]. These effects were attenuated by low salt and normal salt diets which also decreased the ratio of renal ACE/ACE2 expression [29•].…”

Section: Hypertensionmentioning

confidence: 99%

“…Recent studies showed that high-salt diet in spontaneously hypertensive rats decreased ACE2 expression while increasing the ACE/ACE2 ratio, glomerular hypertrophy, loss of the podocytes foot processes, and proteinuria [29•]. These effects were attenuated by low salt and normal salt diets which also decreased the ratio of renal ACE/ACE2 expression [29•]. While these findings imply that changes in ACE/ACE2 ratio may be responsible for hypertensive changes, this study unexpectedly found no difference in ACE or ACE2 activity during high salt intake despite an increase in ACE expression [29•].…”

Section: Hypertensionmentioning

confidence: 99%

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Intrarenal Angiotensin-Converting Enzyme: the Old and the New

Culver

Siragy

2017

Curr Hypertens Rep

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Purpose of Review The intrarenal renin-angiotensin-aldosterone system (RAS) is an independent paracrine hormonal system with an increasingly prominent role in hypertension and renal disease. Two enzyme components of this system are angiotensin-converting enzyme (ACE) and more recently discovered ACE2. The purpose of this review is to describe recent discoveries regarding the roles of intrarenal ACE and ACE2 and their interaction. Recent Findings Renal tubular ACE contributes to salt-sensitive hypertension. Additionally, the relative expression and activity of intrarenal ACE and ACE2 are central to promoting or inhibiting different renal pathologies including renovascular hypertension, diabetic nephropathy, and renal fibrosis. Summary Renal ACE and ACE2 represent two opposing axes within the intrarenal RAS system whose interaction determines the progression of several common disease processes. While this relationship remains complex and incompletely understood, further investigations hold the potential for creating novel approaches to treating hypertension and kidney disease.

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Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

Cited by 30 publications

References 52 publications

Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet

Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet

Effects of controlled doses of Oxyelite Pro on physical performance in rats

Intrarenal Angiotensin-Converting Enzyme: the Old and the New

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