Olmesartan Ameliorates Progressive Glomerular Injury in Subtotal Nephrectomized Rats through Suppression of Superoxide Production

Fujimoto, Sohachi; Satoh, Minoru; Horike, Hideyuki; Hatta, Hidekazu; Haruna, Yoshisuke; Kobayashi, Shinya; Namikoshi, Tamehachi; Arakawa, Sayaka; Tomita, Naruya; Kashihara, Naoki

doi:10.1291/hypres.31.305

Cited by 50 publications

(50 citation statements)

References 42 publications

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“…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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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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“…21,30 Briefly, total RNA was extracted from the aorta with TRIzol (Invitrogen, Tokyo, Japan). Reverse transcriptase reactions were performed using a Ready-To-Go T-Primed First-Strand Kit (Amersham Biosciences, Piscataway, NJ, USA).…”

Section: Real-time Quantitative Pcrmentioning

confidence: 99%

Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy

et al. 2009

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It is important to consider a strategy to halt the development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Oral adsorbent AST-120 retards deterioration in renal function, reducing indoxyl sulfate (IS) accumulation. The aim of this study was to determine whether AST-120 improves endothelial dysfunction by reducing oxidative/nitrative stress in a rat-CKD model. Subtotally nephrectomized (Nx) rats aged 17 weeks were divided into two groups: control rats and rats orally treated with AST-120. Two weeks after initiation of AST-120, serum and urinary IS levels, renal histological scores and endothelium-dependent vascular responses (EDVRs) in the aorta were investigated. EDVR in 5-h incubation with 250 lg ml À1 IS was also examined in normal rat aortas. Nitrotyrosine content, mRNA expression of p47phox, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component, and expression and phosphorylation (serine-1177) of endothelial nitric oxide synthase (eNOS) in the aorta were examined in untreated and treated Nx rats. At the end of treatment, renal function and histological scores were not different in the two groups. AST-120 prevented the elevation of serum IS level in Nx rats, reducing urinary IS excretion, and ameliorated decreased EDVR in Nx rats. Incubation with IS tended to reduce EDVR in normal aortas, albeit insignificantly. AST-120 also suppressed nitrotyrosine accumulation and inhibited p47phox expression in Nx rats. The eNOS expression and phosphorylation were similar in the two groups. In conclusion, AST-120 ameliorated endothelial dysfunction and alleviated oxidative/nitrative stress in the aorta through reduced accumulation of IS, independent of renal function, in a rat CKD model.

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“…The severity of glomerular lesions was graded with a score of 0-3 based on the percentage of glomerular involvement, as described previously. 18 Fluorescence spectrometric assay of O 2 -production in the renal cortex…”

Section: Glomerular Damage Scorementioning

confidence: 99%

“…Angiotensin receptor blockade (ARB) was demonstrated to decrease NADPH oxidase activity. 18 Therefore, reduction of NADPH oxidase activity by ARB seems the most efficient method to improve endothelial function through NOS recoupling. However, the abnormal feature in DS rats is characterized by the dysfunction of NO system.…”

Section: Ds-h Ds-l Ds-h-tel Ds-h-mentioning

confidence: 99%

Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats

et al. 2009

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Hypertensive vascular disorders are characterized by endothelial dysfunction. Loss of renal autoregulation causes glomerular hypertension. However, the relationship between the autoregulatory response and glomerular damage has not been well examined. We examined the contributions of uncoupled endothelial nitric oxide synthase (eNOS) in hypertensive renal disease, and the relationship between the degree of autoregulation impairment and glomerular injury. We also investigated the effects of telmisartan on eNOS coupling and renal autoregulation. Male Dahl salt-sensitive hypertensive (DS) rats (14-week old) fed an 8% salt diet were used to examine endothelial dysfunction and impaired renal autoregulation caused by glomerular hypertension. Some DS rats were treated with telmisartan (3.0 mg kg À1 day À1 ), an angiotensin receptor blocker, for 2 weeks. Increased superoxide production and decreased nitric oxide production, as detected by fluorescent indicator perfusion methods, were observed in the glomeruli and arterioles of hypertensive DS rats. Telmisartan improved the imbalance of superoxide and nitric oxide in the glomeruli and arterioles. Decreased serum tetrahydrobiopterin levels and coupled eNOS seen in the DS rat kidney were improved with telmisartan treatment. The endothelial relaxation reaction was impaired in DS rat aortic arteries. Autoregulatory capacity in response to step changes in perfusion pressure was also impaired in DS rat kidney. Treatment with telmisartan improved these abnormalities. Endothelial dysfunction in the glomeruli and impaired renal autoregulation, which may cause glomerular sclerosis, were observed in DS rat kidney. Telmisartan treatment improves these dysfunctions in hypertensive renal disease.

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Olmesartan Ameliorates Progressive Glomerular Injury in Subtotal Nephrectomized Rats through Suppression of Superoxide Production

Cited by 50 publications

References 42 publications

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

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

Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy

Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats

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