AT1 receptor blockade is superior to conventional triple therapy in protecting against end-organ damage in Cyp1a1-Ren-2 transgenic rats with inducible hypertension

Vaňourková, Zdeňka; Kramer, Herbert J.; Husková, Zuzana; Vaněčková, Ivana; Opočenský, Martin; Chábová, Věra Čertíková; Tesař, Vladimı́r; Škaroupková, Petra; Thumová, Monika; Dohnalova, Michaela; Mullins, John J.; Červenka, Luděk

doi:10.1097/01.hjh.0000251909.00923.22

Cited by 42 publications

(75 citation statements)

References 34 publications

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“…Therefore, in the present study, Ang II and Ang(1-7) levels were determined in plasma and in nonclipped kidneys and hearts in separate experimental groups of the above-described mice (n = 8 in each group). At the end of the experiments (on day 26 after clip placement or sham operation), mice were sacrificed by decapitation, and plasma and tissue Ang II levels were assessed by radioimmunoassay (RIA) based on the procedure developed by Fox et al [30] and further modified and validated in our laboratory [4,5,14,27,[31][32][33] . This approach for blood and tissue sampling and Ang II assay, which is routinely used in our laboratory, allows us to compare the present results with those of our previous studies evaluating the role of RAS in the pathophysiology of hypertension [4,5,14,27,[31][32][33] .…”

Section: Series 3: Determinations Of Plasma and Kidney Tissue Ang II mentioning

confidence: 99%

Knockout of Angiotensin 1–7 Receptor Mas Worsens the Course of Two-Kidney, One-Clip Goldblatt Hypertension: Roles of Nitric Oxide Deficiency and Enhanced Vascular Responsiveness to Angiotensin II

Rakušan

Bürgelová

Vaněčková

et al. 2010

Kidney Blood Press Res

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Aims: The present study was performed to evaluate the effects of target disruption of the G-protein-coupled receptor Mas for angiotensin 1–7 [Ang(1–7)] in knockout mice on the course of two-kidney, one-clip (2K1C) Goldblatt hypertension. Methods: Knockout and wild-type mice underwent clipping of one renal artery. Blood pressure (BP) was monitored by radiotelemetry. The mice were either untreated or chronically treated with the superoxide (O₂^–) scavenger tempol (400 mg/l) or the inhibitor of NADPH oxidase apocynin (1 g/l) administered in drinking water. Results: Knockout mice responded to clipping by accelerated increases in BP and the final BP was significantly higher than that in wild-type mice. Chronic treatment with tempol or apocynin elicited similar antihypertensive effects in 2K1C/knockout as in 2K1C/wild-type mice. Acute nitric oxide synthase inhibition caused greater BP increases in 2K1C/wild-type than in 2K1C/knockout mice. Conclusion: Our present findings support the notion that the angiotensin-converting enzyme 2-Ang(1–7)-Mas axis serves as an important endogenous physiological counterbalancing mechanism that partially attenuates the hypertensinogenic actions of the activated renin-angiotensin system. The impairment in this axis may contribute to the deterioration of the course of 2K1C Goldblatt hypertension.

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Section: Series 3: Determinations Of Plasma and Kidney Tissue Ang II mentioning

confidence: 99%

Knockout of Angiotensin 1–7 Receptor Mas Worsens the Course of Two-Kidney, One-Clip Goldblatt Hypertension: Roles of Nitric Oxide Deficiency and Enhanced Vascular Responsiveness to Angiotensin II

Rakušan

Bürgelová

Vaněčková

et al. 2010

Kidney Blood Press Res

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“…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%

“…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: 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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“…14 Activation of the mRen2 gene is underlying the cardiovascular pathology in TGR and IHR so one would expect that IHR develop a similar form of dilated cardiomyopathy when the heart is sufficiently stressed. While myocardial hypertrophy is evident in IHR, even after short-term (<2 weeks) stimulation, 15 detailed information on cardiac function and structure is missing. A recent study reported a lack of cardiac fibrosis after prolonged mRen2 activation in IHR, but did not show data on cardiac function or heart failure.…”

Section: Introductionmentioning

confidence: 99%

“…A recent study reported a lack of cardiac fibrosis after prolonged mRen2 activation in IHR, but did not show data on cardiac function or heart failure. 15 Furthermore, most studies used relatively young animals while a cardiac phenotype is usually more apparent in adult rats.…”

Section: Introductionmentioning

confidence: 99%

Cardiac remodeling during and after renin–angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

Heijnen

Pelkmans

Danser

et al. 2013

J Renin Angiotensin Aldosterone Syst

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This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle. Hypertrophic genes were highly upregulated, whereas in substantial activation a fibrotic response was absent. Four weeks after withdrawal of I3C, (pro)renin levels were normalized in all IHR. While in adult IHR BP returned to normal, hypertension was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin-induced severe hypertension in IHR causes an age-independent fully reversible myocardial concentric hypertrophic remodeling, despite a continued elevated BP in young IHR.

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AT1 receptor blockade is superior to conventional triple therapy in protecting against end-organ damage in Cyp1a1-Ren-2 transgenic rats with inducible hypertension

Cited by 42 publications

References 34 publications

Knockout of Angiotensin 1–7 Receptor Mas Worsens the Course of Two-Kidney, One-Clip Goldblatt Hypertension: Roles of Nitric Oxide Deficiency and Enhanced Vascular Responsiveness to Angiotensin II

Knockout of Angiotensin 1–7 Receptor Mas Worsens the Course of Two-Kidney, One-Clip Goldblatt Hypertension: Roles of Nitric Oxide Deficiency and Enhanced Vascular Responsiveness to Angiotensin II

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

Cardiac remodeling during and after renin–angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

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