Renal denervation reduces glomerular injury by suppressing NAD(P)H oxidase activity in Dahl salt-sensitive rats

Nagasu, Hajime; Satoh, Minoru; Kuwabara, Atsunori; Yorimitsu, Daisuke; Sakuta, Takeo; Tomita, Naruya; Kashihara, Naoki

doi:10.1093/ndt/gfq139

Cited by 39 publications

(30 citation statements)

References 39 publications

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“…One-quarter of each removed kidney was immersed and fixed in 4% paraformaldehyde and then embedded in paraffin. The remainder of each kidney was cut into small pieces, and glomeruli were isolated by mechanical graded sieving [17] for superoxide production assay, NAD(P)H oxidase activity assay, and mRNA extraction.…”

Section: Methodsmentioning

confidence: 99%

“…Primers and probes for TaqMan analysis were designed using Primer Express 1.5 (Applied Biosystems) with information from the supplier based on the sequence information from GenBank or EST databases. We have previously described the primers and probes used for gp91 phox, p22 phox , p47 phox , p67 phox (where phox indicates phagocyte oxidase), and angiotensin II type 1 receptor (AT1R) [12,17]. Primer and probe sequences for rat ICAM-1 (NM 012967) were as follows: 5′-GAATCCAGCCCCTAATCTGA-3′ (forward primer); 5′-TAAAGGCACGGCACTTGTAG-3′ (reverse primer); and 5′-FAM-CTGCCTATCGGGATGGTGAAGTCTG-TAMRA-3′ (TaqMan probe).…”

Section: Methodsmentioning

confidence: 99%

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Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change

Kidokoro¹,

Satoh²,

Nagasu³

et al. 2012

Kidney Blood Press Res

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Background/Aims: The immunosuppressive drug tacrolimus (FK506) is used clinically to reduce the rejection rate in patients with kidney transplantation; however, the resultant nephrotoxicity remains a serious problem. In the present study we attempted to elucidate the mechanisms of glomerular injury induced by FK506 and the renoprotective effects of the angiotensin II receptor blocker telmisartan. Methods: Seven-week-old male Wistar rats were divided into three groups: vehicle group, FK506 group, and FK506 + telmisartan group. After 8 weeks, we assessed kidney function and renal morphological changes including oxidative stress. We also assessed the effect of FK506 in human glomerular endothelial cells (hGECs) with regard to reactive oxygen species (ROS). Results: FK506 induced ROS production via activation of NAD(P)H oxidase in the glomeruli. Expression of ICAM mRNA was increased in glomeruli from the FK506 group. These effects resulted in macrophage infiltration into the glomeruli. FK506 directly promoted NAD(P)H oxidase activity and accelerated production of ROS in hGECs. Conversely, cotreatment with telmisartan inhibited both NAD(P)H oxidase activity and production of ROS. Conclusion: These findings suggest that glomerular injury resulting from FK506 is caused by oxidative stress mediated by activation of NAD(P)H oxidase and that telmisartan exerts a renoprotective effect via antioxidative activity.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change

Kidokoro¹,

Satoh²,

Nagasu³

et al. 2012

Kidney Blood Press Res

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“…The integrated density (density 3 area) of the bands was quantified using Image-J software (http://rsbweb. nih.gov/ij/) (20). Statistical analysis.…”

Section: Animalsmentioning

confidence: 99%

Endothelial dysfunction promotes the transition from compensatory renal hypertrophy to kidney injury after unilateral nephrectomy in mice

Nagasu

Satoh

Kidokoro

et al. 2012

American Journal of Physiology-Renal Physiology

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Loss of functional nephrons associated with chronic kidney disease induces glomerular hyperfiltration and compensatory renal hypertrophy. We hypothesized that the endothelial nitric oxide synthase (eNOS) [soluble guanylate cyclase (sGC)] protein kinase G (PKG) pathway plays an important role in compensatory renal hypertrophy after unilateral nephrectomy. Analysis of mice subjected to unilateral nephrectomy showed increases in kidney weight-to-body weight and total protein-to-DNA ratios in wild-type but not eNOS knockout (eNOSKO) mice. Serum creatinine and blood urea nitrogen increased after nephrectomy in eNOSKO but not in wild-type mice. Furthermore, Bay 41–2272, an sGC stimulator, induced compensatory renal hypertrophy in eNOSKO mice and rescued renal function. The NO donor S-nitrosoglutathione (GSNO) and Bay 41–2272 stimulated PKG activity and induced phosphorylation of Akt protein in human proximal tubular cells. GSNO also induced phosphorylation of eukaryotic initiation factor 4E-binding protein and ribosomal protein S6. Our results highlight the importance of the eNOS-NO-PKG pathway in compensatory renal hypertrophy and suggest that reduced eNOS-NO bioavailability due to endothelial dysfunction is the underlying mechanism of failure of compensatory hypertrophy and acceleration of progressive renal dysfunction.

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“…Renal denervation was performed as described previously. 20 The SBP and heart rate were measured every week by the tail-cuff method. After 3 weeks, urine was collected over 24 h to measure proteinuria and oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA), and each rat was anesthetized with sevoflurane.…”

Section: Chronic Administration Of Amlodipine and Azelnidipinementioning

confidence: 99%

“…A piece of kidney tissue was used for measurement of norepinephrine concentration as described previously. 20 Total RNA isolation, reverse transcriptase reactions and real-time quantitative polymerase chain reactions for angiotensinogen and angiotensin type 1 receptor were performed as described previously. 23 The change in the expression was expressed by standardizing RNA levels corrected for glyceraldehyde-3-phosphate dehydrogenase expression in the sample.…”

Section: Chronic Administration Of Amlodipine and Azelnidipinementioning

confidence: 99%

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity

et al. 2011

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Dihydropyridine-type calcium channel blockers (CCBs) exert potent antihypertensive effects. The CCB azelnidipine decreases heart rate by suppressing sympathetic nerve activity, which affects afferent and efferent arterioles in the glomeruli. We examined whether azelnidipine can improve progressive glomerular injury in comparison with amlodipine by suppressing renal sympathetic nerve activity in Dahl salt-sensitive rats. Glomerular circulation in Dahl salt-sensitive rats was monitored with a charge-coupled device camera before and after administration of amlodipine (0.5 mg kg À1 , bolus injection) or azelnidipine (0.1 mg kg À1 , bolus injection). Systemic sympathetic nerve activity was also compared by analysis of heart rate variability with a telemetry blood pressure monitoring system after crossover administration of amlodipine (1.0 mg kg À1 per day) and azelnidipine (3.0 mg kg À1 per day) for 1 week. To investigate renoprotective effects, rats were treated with amlodipine (1.0 mg kg À1 per day) or azelnidipine (3.0 mg kg À1 per day) for 3 weeks with or without renal denervation. The efferent arteriole contracted in response to acute amlodipine but not azelnidipine treatment. The low frequency/high frequency ratio, an index of parasympathetic nerve activity, decreased in response to azelnidipine but not amlodipine treatment. In response to chronic treatment, proteinuria and glomerular injury improved to a greater extent with azelnidipine compared with amlodipine. The renoprotective effects of azelnidipine were diminished by renal denervation. Azelnidipine decreased glomerular damage in Dahl salt-sensitive rats to a greater extent than amlodipine. Azelnidipine appeared to decrease intraglomerular pressure by suppressing sympathetic nerve activity.

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Renal denervation reduces glomerular injury by suppressing NAD(P)H oxidase activity in Dahl salt-sensitive rats

Abstract: Renal sympathetic denervation helps to protect against glomerular sclerosis, possibly by suppressing NAD(P)H oxidase activity, thereby decreasing glomerular reactive oxygen species.

Cited by 39 publications

References 39 publications

Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change

Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change

Endothelial dysfunction promotes the transition from compensatory renal hypertrophy to kidney injury after unilateral nephrectomy in mice

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity

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