Regression of left ventricular hypertrophy and aortic remodelling in NO‐deficient hypertensive rats: effect of l‐arginine and spironolactone

Paulis, Ludovít; Matusková, Jana; Adamcová, Michaela; Pelouch, V.; Simko, J; Krajcirovicova, Kristina; Potáčová, Anna; Hulín, I; Janega, Pavol; Pecháňová, Oľga; Šimko, Fedor

doi:10.1111/j.1748-1716.2008.01862.x

Cited by 30 publications

(27 citation statements)

References 40 publications

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“…In the present study we observed that aortic remodeling in L-NAME hypertension was characterized by increased aortic WT similarly to our previous studies. 25 The wall thickening was accompanied by reduced ID, slightly increased aortic cross-sectional area, and most importantly increased WT/ID ratio in accordance with previous studies on this model of hypertension. 27,48 In our study we have investigated the effects of the AT 2 R agonist on PWV in L-NAME rats.…”

Section: Discussionsupporting

confidence: 78%

“…The effect of L-NAME administration on BP was reported in numerous studies by our laboratory [31][32][33] and others. 22,23,26 L-NAME-induced hypertension is associated with target organ damage, such as cardiac hypertrophy and fibrosis, 33 vascular remodeling, 25 and endothelial damage. 26 Current European guidelines also regard augmented PWV as an indicator of subclinical organ damage.…”

Section: Discussionmentioning

confidence: 99%

“…AT 2 R was already reported to exert antiproliferative, anti-inflammatory, and cardioprotective effects that at least partly counterbalance the effects of AT 1 R stimulation. 16 -21 In vivo inhibition of NO synthase by treating animals with N -nitro-L-arginine-methyl ester (L-NAME) provides a wellestablished model of hypertension, [22][23][24] vascular wall remodeling, 25,26 and PWV increase. 27,28 Using this model, we aimed to investigate the effects of long-term direct AT 2 R stimulation by the novel nonpeptide AT 2 R agonist, compound 21, on aortic remodeling and PWV in L-NAME-treated rats.…”

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confidence: 99%

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Direct Angiotensin II Type 2 Receptor Stimulation in N ^ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

et al. 2012

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Abstract-Pulse wave velocity (PWV), a direct marker of arterial stiffness, is an independent cardiovascular risk factor.Although the angiotensin II type 1 receptor blockade belongs to major antihypertensive and cardioprotective therapies, less is known about the effects of long-term stimulation of the angiotensin II type 2 receptor. Previously, compound 21, a selective nonpeptide angiotensin II type 2 receptor agonist improved the outcome of myocardial infarction in rats along with anti-inflammatory properties. We investigated whether compound 21 alone or in combination with angiotensin II type 1 receptor blockade by olmesartan medoxomil could prevent PWV increase and aortic remodeling in N -nitro-L-argininemethyl ester (L-NAME)-induced hypertension. Male adult Wistar rats (nϭ65) were randomly assigned to control, L-NAME, L-NAMEϩcompound-21, L-NAMEϩolmesartan, and L-NAMEϩolmesartanϩcompound-21 groups and treated for 6 weeks. We observed that L-NAME hypertension was accompanied by enhanced PWV, increased wall thickness, and stiffness of the aorta, along with elevated hydroxyproline concentration. Olmesartan completely prevented hypertension, PWV and wall thickness increase, and the increase of aortic stiffness and partly prevented hydroxyproline accumulation. Compound 21 partly prevented all of these alterations, yet without concomitant prevention of blood pressure rise. Although the combination therapy with olmesartan and compound 21 led to blood pressure levels, PWV, and wall thickness comparable to olmesartan-alone-treated rats, only in the combination group was complete prevention of increased hydroxyproline deposition achieved, resulting in even more pronounced stiffness reduction. We conclude that chronic angiotensin II type 2 receptor stimulation prevented aortic stiffening and collagen accumulation without preventing hypertension in rats with inhibited NO synthase. These effects were additive to angiotensin II type 1 receptor blockade, yet without additional blood pressurelowering effect, and they seem to be NO and blood pressure independent. Key Words: L-NAME Ⅲ vascular remodeling Ⅲ arterial stiffness Ⅲ pulse wave velocity Ⅲ renin-angiotensin system Ⅲ hypertension A rterial hypertension is a highly prevalent and still insufficiently controlled medical condition leading to severe cardiovascular complications. 1,2 One of the main contributors to the cardiovascular risk in these patients is the associated target organ damage. Augmented pulse wave velocity (PWV), which is considered to be the best and direct marker of arterial stiffness, 3 is regarded as an indicator of subclinical organ damage by current European guidelines for hypertension treatment. 4 The effects of current antihypertensive treatment on PWV have been investigated with various outcomes. The angiotensin II type 1 receptor (AT 1 R) antagonists, together with angiotensin-converting enzyme inhibitors, belong to the gold standard cardioprotective therapies. 5,6 In a study on 113 hypertensives, 2-to 3-year treatment with candesartan produced a l...

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Direct Angiotensin II Type 2 Receptor Stimulation in N ^ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

et al. 2012

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“…In another study, TERalb was higher in atherosclerotic patients, however, was not different between normotensive and hypertensive subjects (Pedrinelli et al 1998). In contrast, another study demonstrated that endothelial permeability was higher in hypertensive subjects, but endothelium-dependent relaxation was not different in uncomplicated mild to moderate hypertension (Paulis et al 2008). We also found that reversal of hypertension did not alter endothelial permeability.…”

Section: Discussionsupporting

confidence: 55%

Effect of hypertension and its reverse on serum nitric oxide concentration and vascular permeability in two-kidney one-clip hypertensive rats

Khazaei¹,

Zarei²,

Sharifi³

et al. 2011

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Abstract. The aim of this study was to evaluate the effect of hypertension and its reverse on serum nitric oxide (NO) concentration and endothelial permeability in two-kidney one-clip (2K1C) hypertensive rats. 28 male Wistar rats were divided into four groups: 1) 2K1C for 12 weeks; 2) sham-clipped for 12 weeks; 3) 2K1C for 12 weeks and unclipped for 12 weeks; 4) sham-clipped for 12 weeks and unclipped for 12 weeks. Blood samples were taken before experiment, 12 th week and 24 th week (in groups 3 and 4). Coronary vascular and aortic endothelial permeability were determined by extravasation of Evans blue dye method. Serum NO level was significantly lower in hypertensive group compare with sham group (4.21 ± 1.28 vs. 9.47 ± 1.34 µmol/l, respectively). Reversal of hypertension did not improve serum NO concentration in 2K1C group (4.21 ± 1.28 vs. 4.32 ± 1.34 µmol/l). Coronary vascular and aortic endothelial permeability were not different between hypertensive and normotensive groups and reversal of hypertension did not alter endothelial permeability. Lower serum NO concentration in 2K1C hypertensive rats even after reversal of hypertension suggested that in addition to NO, other mechanisms could be involved in surgical reversal of hypertension. Hypertension and its reverse did not change endothelial permeability at least in this model of hypertension.

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“…Further study is needed to fully elucidate the pathways involved. However, several circulating factors, including asymmetric dimethyl arginine (35,36), parathyroid hormone (37), aldosterone (38), fibroblast growth factor-23 (39), angiotensin-2 (40), endogenous cardiac glycosides (41), vitamin D (42), and circulating angiogenesis inhibitors, have been implicated (35).…”

Section: Pathophysiology Of Arrhythmia In Ckdmentioning

confidence: 99%

Arrhythmia and Sudden Death in Hemodialysis Patients

Charytan

Foley

McCullough

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background Dialysis patients have high rates of cardiovascular morbidity and mortality, but data on arrhythmia burden, arrhythmia type, arrhythmia triggers, and the identity of terminal arrhythmias have historically been limited by an inability to monitor heart rhythm for prolonged periods.Objectives To investigate arrhythmia and its association with sudden death in dialysis-dependent ESRD, describe the potential for implantable devices to advance study of dialysis physiology, review the ethical implications of using implantable devices in clinical studies, and report on the protocol and baseline results of the Monitoring in Dialysis Study (MiD).Design, setting, participants, & measurements In this multicenter, interventional-observational, prospective cohort study, we placed implantable loop recorders in patients undergoing long-term hemodialysis. The proportion of patients experiencing clinically significant arrhythmias was the primary endpoint. For 6 months, we captured detailed data on the primary endpoint, symptomatic arrhythmias, other electrocardiographic variables, dialysis prescription, electrolytes, dialysis-related variables, and vital signs. We collected additional electrocardiographic data for up to 1 year.Results Overall, 66 patients underwent implantation in sites in the United States and India. Diabetes was present in 63.6% of patients, 12.1% were age $70 years, 69.7% were men, and 53.0% were black. Primary and secondary endpoint data are expected in 2016.Conclusions Cardiac arrhythmia is an important contributor to cardiovascular morbidity and mortality in dialysis patients, but available technology has previously limited the ability to estimate its true burden and triggers and to define terminal rhythms in sudden death. Use of implantable technology in observational studies raises complex issues but may greatly expand understanding of dialysis physiology. The use of implantable loop recorders in MiD is among the first examples of such a trial, and the results are expected to provide novel insights into the nature of arrhythmia in hemodialysis patients.

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Regression of left ventricular hypertrophy and aortic remodelling in NO‐deficient hypertensive rats: effect of l‐arginine and spironolactone

Cited by 30 publications

References 40 publications

Direct Angiotensin II Type 2 Receptor Stimulation in N ^ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

Direct Angiotensin II Type 2 Receptor Stimulation in N ^ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

Effect of hypertension and its reverse on serum nitric oxide concentration and vascular permeability in two-kidney one-clip hypertensive rats

Arrhythmia and Sudden Death in Hemodialysis Patients

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Regression of left ventricular hypertrophy and aortic remodelling in NO‐deficient hypertensive rats: effect of l‐arginine and spironolactone

Cited by 30 publications

References 40 publications

Direct Angiotensin II Type 2 Receptor Stimulation in N ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

Direct Angiotensin II Type 2 Receptor Stimulation in N ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

Effect of hypertension and its reverse on serum nitric oxide concentration and vascular permeability in two-kidney one-clip hypertensive rats

Arrhythmia and Sudden Death in Hemodialysis Patients

Contact Info

Product

Resources

About

Direct Angiotensin II Type 2 Receptor Stimulation in N ^ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

Direct Angiotensin II Type 2 Receptor Stimulation in N ^ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension