The role of intrarenal angiotensin II in the development of hypertension in Ren-2 transgenic rats

Kopkan, Libor; Kramer, Herbert J.; Husková, Zuzana; Vaňourková, Zdeňka; Škaroupková, Petra; Thurmová, Monika; Červenka, Luděk

doi:10.1097/01.hjh.0000174972.46663.5e

Cited by 32 publications

(77 citation statements)

References 26 publications

(58 reference statements)

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“…In this study, we utilized the transgenic Ren2 rat that harbors the mouse Ren-2 d renin gene and exhibits elevated serum renin and tissue Ang II levels [17][18][19] to explore the relationship between the RAS and the development of NAFLD. Our investigation reveals novel findings:…”

Section: Discussionmentioning

confidence: 99%

“…However, to date, there is no published study using a genetic model with excessive activity of RAS to directly evaluate its role on the development and progression of hepatic steatosis, inflammation and fibrosis. The transgenic TG(mRen2)27 (Ren2) rat harbors the mouse Ren-2 d renin gene and exhibits elevated renin and Ang II levels [17][18][19] with subsequent fulminant hypertension [20]. Thus, the Ren2 rat provides a unique animal model to directly explore the role of chronic endogenous elevations of tissue Ang II on the development of NAFLD.…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats

Wei

Clark

Morris

et al. 2008

Journal of Hepatology

106

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Background/Aims-Non-alcoholic fatty liver disease (NAFLD) is a common health problem and includes a spectrum of hepatic steatosis, steatohepatitis and fibrosis. The renin-angiotensin system (RAS) plays a vital role in blood pressure regulation and appears to promote hepatic fibrogenesis. We hypothesized that increased RAS activity causes NAFLD due to increased hepatic oxidative stress.Methods-We employed the transgenic TG(mRen2)27(Ren2) hypertensive rat, harboring the mouse renin gene with elevated tissue Angiotensin II (Ang II).Results-Compared with normotensive Sprague-Dawley (SD) control rats, Ren2 developed significant hepatic steatosis by 9 weeks of age that progressed to marked steatohepatitis and fibrosis by 12 weeks. These changes were associated with increased levels of hepatic reactive oxygen species (ROS) and lipid peroxidation. Accordingly, 9-week-old Ren2 rats were treated for 3 weeks with valsartan, an angiotensin type 1 receptor blocker, or tempol, a superoxide dismutase/catalase mimetic. Hepatic indices for oxidative stress, steatosis, inflammation and fibrosis were markedly attenuated by both valsartan and tempol treatment.Conclusions-This study suggests that Ang II causes development and progression of NAFLD in the transgenic Ren2 rat model by increasing hepatic ROS. Our findings also support a potential role of RAS in prevention and treatment of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats

Wei

Clark

Morris

et al. 2008

Journal of Hepatology

106

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“…In view of these previous observations that the largest amount of ANG II-like immunoreactivity on HPLC coeluted with ANG II and given the high specificity of the ANG II antisera [37] , the individual plasma and kidney samples obtained in the present study were not subjected to HPLC prior to the RIA. This methodological approach was validated by Mitchell et al [8] and since that time we have also employed this method routinely in our laboratory [7,9,17,18,39] . ANG II levels were assessed by RIA using a commercially available kit (EuroDiagnostica Co., Malmö, Sweden).…”

Section: Series 1: Assessment Of Systolic Bp Plasma and Kidney Ang Imentioning

confidence: 91%

“…Thus, we used total tissue ANG II levels as a reliable index of tissue RAS activity. The above described procedure for blood sampling and ANG II assay is routinely employed in our laboratory and this standardized approach allows us to compare the results from our previous studies evaluating the role of the RAS in the pathophysiology of hypertension [7,9,17,18,39] .…”

Section: Series 1: Assessment Of Systolic Bp Plasma and Kidney Ang Imentioning

confidence: 99%

Effects of Dietary Salt Load and Salt Depletion on the Course of Hypertension and Angiotensin II Levels in Male and Female Heterozygous Ren-2 Transgenic Rats

Husková

Kramer

Vaňourková

et al. 2007

Kidney Blood Press Res

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Background: In the present study we evaluated plasma and kidney angiotensin II (ANG II) levels in female and male Ren-2 transgenic rats (TGR) in comparison to age-matched female and male normotensive Hannover Sprague-Dawley rats. Methods: The rats were maintained on a normal sodium (NS) diet (0.6% NaCl) or fed a high sodium (HS) diet (2% NaCl) for 4 days or were sodium depleted by administration of 40 mg furosemide per liter drinking water overnight followed by 3 days of low sodium diet (0.01% NaCl) (LS + F). ANG II levels were determined by radioimmunoassay. Results: Female TGR at the age of 38 days were already hypertensive and had developed cardiac hypertrophy, whereas male TGR at this age still exhibited a normotensive phenotype. HS diet increased the blood pressure (BP) but did not alter the ANG II levels in TGR at any age. LS + F decreased the BP without significant change in ANG II concentrations in TGR. Female TGR responded to salt loading and salt depletion by more pronounced changes in BP than male TGR. Conclusions: Female TGR develop hypertension more rapidly and the salt-sensitive component of hypertension is more pronounced in female than in male TGR.

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“…Plasma was separated and eluted in ethanol, centrifuged, evaporated using Savant Speed Vac and stored at -80 ° C until assayed. Plasma and tissue ANG II levels were assessed by radioimmunoassay as described in detail previously [22] . …”

Section: Plasma and Tissue Ang II Concentrationsmentioning

confidence: 99%

Long-Term Prevention of Hypertension and End-Organ Damage in Ren-2 Transgenic Rats Is Achieved Only with Persistent but Not Transient AT<sub>1 </sub>Receptor Blockade

Vaněčková

Kopkan²,

Husková³

et al. 2007

Kidney Blood Press Res

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The aim of this study was first to evaluate the effects of persistent or transient blockade of the angiotensin II (ANG II) receptor AT₁ on the development of hypertension and end-organ damage in hypertensive Ren-2 transgenic rats (TGR), and second to assess the potential role of AT₂ receptors in the control of blood pressure (BP) in this monogenetic model of hypertension. Male heterozygous TGR and Hannover Sprague-Dawley (HanSD) rats fed a normal salt diet were treated from day 32 of age either persistently until the end of the experiment (day 100 of age) or transiently until day 56 of age with the selective AT₁ receptor antagonist candesartan or with the combination of candesartan and the AT₂ receptor antagonist PD 123319. Persistent treatment with candesartan completely prevented the rise in BP, proteinuria and the increase in left ventricular weight/body weight ratio, whereas transient treatment with candesartan was effective only as long as the drug was administered. In the presence of candesartan, PD 123319 was without effect. Our results show that in male heterozygous TGR persistent candesartan treatment completely prevented hypertension and end-organ damage as long as the drug was administered, whereas transient AT₁receptor blockade had no long-term effects.

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The role of intrarenal angiotensin II in the development of hypertension in Ren-2 transgenic rats

Cited by 32 publications

References 26 publications

Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats

Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats

Effects of Dietary Salt Load and Salt Depletion on the Course of Hypertension and Angiotensin II Levels in Male and Female Heterozygous Ren-2 Transgenic Rats

Long-Term Prevention of Hypertension and End-Organ Damage in Ren-2 Transgenic Rats Is Achieved Only with Persistent but Not Transient AT<sub>1 </sub>Receptor Blockade

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