High-sodium diet promotes a profibrogenic reaction in normal rat kidneys: effects of Tempol administration

Rosón, María Inés; Lorena, Silvana; Penna, Della; Cao, Gabriel; Gorzalczany, Susana; Pandolfo, Marcela; Cerrudo, Carolina Susana; Fernández, Belisario E.; Toblli, Jorge Eduardo

doi:10.5301/jn.2010.5824

Cited by 18 publications

(26 citation statements)

References 13 publications

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“…Salt may induce myocardial and renal fibrosis in normotensive and hypertensive rats in coincidence with oxidative stress (41) and upregulation of TGF-␤1 mRNA (59), and an increase in renal expression and urinary excretion of TGF-␤ has also been described in the renal cortex of Sprague-Dawley rats submitted to a high-sodium diet without a significant increase in blood pressure (57,58).…”

Section: Discussionmentioning

confidence: 94%

Antihypertensive and renoprotective effect of the kinin pathway activated by potassium in a model of salt sensitivity following overload proteinuria

Ardiles

Cárdenas

Burgos

et al. 2013

American Journal of Physiology-Renal Physiology

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The albumin overload model induces proteinuria and tubulointersitial damage, followed by hypertension when rats are exposed to a hypersodic diet. To understand the effect of kinin system stimulation on salt-sensitive hypertension and to explore its potential renoprotective effects, the model was induced in Sprague-Dawley rats that had previously received a high-potassium diet to enhance activity of the kinin pathway, followed with/without administration of icatibant to block the kinin B₂ receptor (B₂R). A disease control group received albumin but not potassium or icatibant, and all groups were exposed to a hypersodic diet to induce salt-sensitive hypertension. Potassium treatment increased the synthesis and excretion of tissue kallikrein (Klk1/rKLK1) accompanied by a significant reduction in blood pressure and renal fibrosis and with downregulation of renal transforming growth factor-β (TGF-β) mRNA and protein compared with rats that did not receive potassium. Participation of the B₂R was evidenced by the fact that all beneficial effects were lost in the presence of the B₂R antagonist. In vitro experiments using the HK-2 proximal tubule cell line showed that treatment of tubular cells with 10 nM bradykinin reduced the epithelial-mesenchymal transdifferentiation and albumin-induced production of TGF-β, and the effects produced by bradykinin were prevented by pretreatment with the B₂R antagonist. These experiments support not only the pathogenic role of the kinin pathway in salt sensitivity but also sustain its role as a renoprotective, antifibrotic paracrine system that modulates renal levels of TGF-β.

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Section: Discussionmentioning

confidence: 94%

Antihypertensive and renoprotective effect of the kinin pathway activated by potassium in a model of salt sensitivity following overload proteinuria

Ardiles

Cárdenas

Burgos

et al. 2013

American Journal of Physiology-Renal Physiology

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“…Tempol, has been shown to reduce oxidative stress and attenuate hypertension in obese Zucker rats, Dahl salt-sensitive and spontaneously hypertensive rats (SHR)[34-38]. In addition, we have previously reported that tempol can prevent the increase in renal oxidative stress and arterial pressure in Sprague Dawley rats fed a high salt diet[7]. …”

Section: Discussionmentioning

confidence: 99%

“…It is well known that a high salt intake increases the oxidative stress in the kidney of normal and salt-sensitive rats[3-5]. In this regard, we have reported that the administration of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine- N -oxyl), a permeate superoxide dismutase mimetic[6] commonly used to scavenge superoxide anion, prevented oxidative stress and produced a natriuretic and diuretic effect in Sprague Dawley rats fed a high salt diet[7]. …”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, a local RAS that is expressed in the kidneys and operate independently of the systemic RAS, may also contribute to long-term blood pressure control and cause renal injury when it is associated with a high salt diet[7,9-11]. Angiotensin II (Ang II), the main effector of RAS, acts through two receptor subtypes named angiotensin II type-1 receptor (AT1R) and type-2 receptor (AT2R).…”

Section: Introductionmentioning

confidence: 99%

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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

Self Cite

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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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“…In addition to these mechanisms, oxidative stress also induces inflammation and fibrosis within the kidney which ultimately facilitates the development of hypertension. In the presence of the SOD mimetic Tempol, rats exposed to a high-salt diet showed an amelioration of hypertension which is most likely linked to the prevention of renal inflammation and fibrosis by reducing renal oxidative stress and improving sodium excretion (Roson et al, 2011). …”

Section: Oxidative Stress In the Pathogenesis Of Hypertensionmentioning

confidence: 99%

Systemic and renal oxidative stress in the pathogenesis of hypertension: modulation of long-term control of arterial blood pressure by resveratrol

Hamza

Dyck

2014

Front. Physiol.

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Hypertension affects over 25% of the global population and is associated with grave and often fatal complications that affect many organ systems. Although great advancements have been made in the clinical assessment and treatment of hypertension, the cause of hypertension in over 90% of these patients is unknown, which hampers the development of targeted and more effective treatment. The etiology of hypertension involves multiple pathological processes and organ systems, however one unifying feature of all of these contributing factors is oxidative stress. Once the body's natural anti-oxidant defense mechanisms are overwhelmed, reactive oxygen species (ROS) begin to accumulate in the tissues. ROS play important roles in normal regulation of many physiological processes, however in excess they are detrimental and cause widespread cell and tissue damage as well as derangements in many physiological processes. Thus, control of oxidative stress has become an attractive target for pharmacotherapy to prevent and manage hypertension. Resveratrol (trans-3,5,4′-Trihydroxystilbene) is a naturally occurring polyphenol which has anti-oxidant effects in vivo. Many studies have shown anti-hypertensive effects of resveratrol in different pre-clinical models of hypertension, via a multitude of mechanisms that include its function as an anti-oxidant. However, results have been mixed and in some cases resveratrol has no effect on blood pressure. This may be due to the heavy emphasis on peripheral vasodilator effects of resveratrol and virtually no investigation of its potential renal effects. This is particularly troubling in the arena of hypertension, where it is well known and accepted that the kidney plays an essential role in the long term regulation of arterial pressure and a vital role in the initiation, development and maintenance of chronic hypertension. It is thus the focus of this review to discuss the potential of resveratrol as an anti-hypertensive treatment via amelioration of oxidative stress within the framework of the fundamental physiological principles of long term regulation of arterial blood pressure.

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High-sodium diet promotes a profibrogenic reaction in normal rat kidneys: effects of Tempol administration

Cited by 18 publications

References 13 publications

Antihypertensive and renoprotective effect of the kinin pathway activated by potassium in a model of salt sensitivity following overload proteinuria

Antihypertensive and renoprotective effect of the kinin pathway activated by potassium in a model of salt sensitivity following overload proteinuria

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

Systemic and renal oxidative stress in the pathogenesis of hypertension: modulation of long-term control of arterial blood pressure by resveratrol

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