Aliskiren attenuates oxidative stress and improves tubular status in non-diabetic patients with chronic kidney disease-Placebo controlled, randomized, cross-over study

Renke, Marcin; Lizakowski, Sławomir; Tylicki, Leszek; Rutkowski, Przemysław; Knap, Narcyz; Heleniak, Zbigniew; Sławińska-Morawska, Maja; Aleksandrowicz−Wrona, Ewa; Januszczyk, Jacek; Wójcik-Stasiak, Małgorzata; Małgorzewicz, Sylwia; Woźniak, Michał; Rutkowski, Bolesław

doi:10.1016/j.advms.2014.03.003

Cited by 15 publications

(15 citation statements)

References 35 publications

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“…On the other hand, the cardiac lesions due to myocardial I/R were found to worsen myocardium biochemical dysfunction, marked by significant increase of LDH and CK in serum . Aliskiren was reported to attenuate oxidative stress in several pathophysiological conditions . In the current study, there were similar infarct size after myocardial I/R injury in WT and eNOS −/− mice, which was consistent with previous reports .…”

Section: Discussionmentioning

confidence: 99%

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

Chen

Meng

Wei

et al. 2017

Clin Exp Pharma Physio

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Aliskiren, a direct renin inhibitor, has shown potent ability to attenuate hypertension. Our previous research has found that aliskiren protected against myocardial ischaemia-reperfusion (I/R) injury and enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in spontaneously hypertensive rats. However, whether the cardioprotective effect of aliskiren against myocardial I/R injury was eNOS-dependent is unknown. In the present study, 12-week-old male eNOS knockout (eNOS ) and wild-type C57BL/6J mice (WT) were orally administrated with the dose of 50 mg/kg per day of aliskiren. After a 4-week treatment, aliskiren decreased blood pressure in eNOS mice, and reduced renin-angiotension II levels in both eNOS and WT mice. Aliskiren also improved left ventricular ejection fraction (EF) and fractional shortening (FS), decreased myocardial infarct size, reduced creatine kinase (CK) and lactate dehydrogenase (LDH) activity in plasma, attenuated dihydroethidium (DHE) fluorescence and levels of malondialdehyde (MDA), enhanced superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) in myocardium, increased SOD and thioredoxin (Trx) proteins expression in WT mice subjected to 30 minutes of ischaemia followed by reperfusion for 24 hours. However, aliskiren failed to restore all of the above indices in eNOS mice subjected to the same I/R injury. Our study indicated that aliskiren protected against myocardial I/R injury via an eNOS dependent manner.

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Section: Discussionmentioning

confidence: 99%

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

Chen

Meng

Wei

et al. 2017

Clin Exp Pharma Physio

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show abstract

“…81,83,87,[110][111][112]377,378 Artery narrowing is already routinely counteracted by renal angioplasty with or without stenting and the administration of vasoconstriction inhibitors that target the renin-angiotensin-aldosterone system. 49,[379][380][381] The targeting of vasoconstriction pathways controlled through vasopressin, endothelin, and voltage dependent calcium channels are in their infancy, as is the use of vasodilators such as arginine and kallikrein. 155,250,268,298,379,382,383 Beyond systemic hypooxygenation and vasoconstriction, the hypoxia-dependent processes of microvascular rarefaction, oxidative stress, leukocyte recruitment, and fibrosis all contribute to the development of CKD.…”

Section: A New Hypoxia Paradigmmentioning

confidence: 99%

Hypoxia: The Force that Drives Chronic Kidney Disease

Colgan

Shelley

2016

Clinical Medicine & Research

128

111

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In the United States the prevalence of end-stage renal disease (ESRD) reached epidemic proportions in 2012 with over 600,000 patients being treated. The rates of ESRD among the elderly are disproportionally high. Consequently, as life expectancy increases and the baby-boom generation reaches retirement age, the already heavy burden imposed by ESRD on the US health care system is set to increase dramatically. ESRD represents the terminal stage of chronic kidney disease (CKD). A large body of evidence indicating that CKD is driven by renal tissue hypoxia has led to the development of therapeutic strategies that increase kidney oxygenation and the contention that chronic hypoxia is the final common pathway to end-stage renal failure. Numerous studies have demonstrated that one of the most potent means by which hypoxic conditions within the kidney produce CKD is by inducing a sustained inflammatory attack by infiltrating leukocytes. Indispensable to this attack is the acquisition by leukocytes of an adhesive phenotype. It was thought that this process resulted exclusively from leukocytes responding to cytokines released from ischemic renal endothelium. However, recently it has been demonstrated that leukocytes also become activated independent of the hypoxic response of endothelial cells. It was found that this endothelium-independent mechanism involves leukocytes directly sensing hypoxia and responding by transcriptional induction of the genes that encode the β2-integrin family of adhesion molecules. This induction likely maintains the long-term inflammation by which hypoxia drives the pathogenesis of CKD. Consequently, targeting these transcriptional mechanisms would appear to represent a promising new therapeutic strategy.

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“…PTX is a clinically available phosphodiesterase inhibitor that has been shown to reduce proteinuria in various human kidney diseases, including mesangial proliferative glomerulonephritis and IgA nephropathy (19)(20)(21)(22)(23)(24). The antiproteinuric effect of this drug is largely ascribed to its inhibitory action on TNF-α and/or TGF-β pathways (20,27,28).…”

Section: Discussionmentioning

confidence: 99%

“…Our data show that the pathogenesis of proteinuria in anti-Thy1 glomerulonephritis involves TNF-α and TGF-β/activin pathways, and the evolution of this process can be attenuated by pentoxifylline via downregulation of NF-κB and Smad signals and restoration of the podocyte component of the glomerular filtration barrier. the potential mechanisms whereby proteinuria developed in anti-Thy1 disease and the modulation of which by selective signal transduction inhibitors, including the known antiproteinuric agent pentoxifylline (PTX) (19)(20)(21)(22)(23)(24).…”

Section: Pentoxifylline Attenuates Proteinuria In Anti-thy1 Glomerulomentioning

confidence: 99%

Pentoxifylline Attenuates Proteinuria in Anti-Thy1 Glomerulonephritis via Downregulation of Nuclear Factor-κB and Smad2/3 Signaling

Chen

Chiang

Yang

et al. 2015

Mol Med

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Aliskiren attenuates oxidative stress and improves tubular status in non-diabetic patients with chronic kidney disease-Placebo controlled, randomized, cross-over study

Cited by 15 publications

References 35 publications

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

Hypoxia: The Force that Drives Chronic Kidney Disease

Pentoxifylline Attenuates Proteinuria in Anti-Thy1 Glomerulonephritis via Downregulation of Nuclear Factor-κB and Smad2/3 Signaling

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