Role of Nitric Oxide–Producing and–Degrading Pathways in Coronary Endothelial Dysfunction in Chronic Kidney Disease

Tatematsu, Satoru; Wakino, Shu; Kanda, Takeshi; Homma, Koichiro; Yoshioka, Kyoko; Hara, Kazuhiro; Sugano, Naoki; Kimoto, Masumi; Saruta, Takao; Hayashi, Kôichi

doi:10.1681/asn.2006040367

Cited by 70 publications

(57 citation statements)

References 47 publications

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“…A previous study reported the presence of high plasma levels of ADMA and reduced endotheliumdependent vasodilatation of coronary arteries in dogs four weeks after uninephrectomy (24). In the present study, however, endothelium-dependent vascular responses of the aorta were not different between the ShamSP and NxSP groups, one week after uninephrectomy.…”

Section: Discussioncontrasting

confidence: 78%

High dietary protein intake induces endothelial dysfunction in uninephrectomized rats

Namikoshi

Tomita²,

Satoh³

et al. 2009

Mol Med Rep

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Abstract. High dietary protein (HP) intake is a risk factor for chronic kidney disease (CKD). HP intake is associated with the development of albuminuria and glomerulosclerosis in uninephrectomized rats. In such rats, we investigated whether HP intake induces endothelial dysfunction. Male Wistar rats were divided into sham-operated rats fed a standard-protein diet, sham-operated rats fed a high-protein diet, uninephrectomized rats fed a standard-protein diet (NxSP) and uninephrectomized rats fed a high-protein diet (NxHP) (n=8 each). One week after treatment, endothelial function and urinary albumin excretion (UAE) were measured. Protein expression, phosphorylation at serine residue 1177 and uncoupling of endothelial nitric oxide synthase (eNOS), and mRNA expression of NADPH oxidase components were assessed in the aorta. NxHP rats showed hypertriglyceridemia and modest hyperhomocysteinemia. Endothelial function was significantly lower, and UAE was significantly higher in NxHP rats compared with the other groups (P<0.01 each), although there was no difference in creatinine clearance between NxSP and NxHP rats. Expression levels, phosphorylation and the dimer/monomer ratio of eNOS did not differ among the four groups. HP intake did not modify p22phox and p47phox expression levels in uninephrectomized rats. In conclusion, HP intake induced endothelial dysfunction and enhanced albuminuria in uninephrectomized rats, independent of renal function, suggesting that HP intake may cause the development of cardiovascular disease associated with CKD.

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Section: Discussioncontrasting

confidence: 78%

High dietary protein intake induces endothelial dysfunction in uninephrectomized rats

Namikoshi

Tomita²,

Satoh³

et al. 2009

Mol Med Rep

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“…28 In a canine model of CKD, the downregulation of dimethylarginine dimethylaminohydrolase-II and endothelial NO synthase lead to blunted coronary vasodilation induced by acetylcholine. 15 Furthermore, CKD is associated with elevated inflammatory factors, hyperhomocysteinemia, oxidant stress, and an activated rennin -angiotensin system, 27,29,30 which also can lead to endothelial dysfunction. Thus, CKD might be associated with the presence of VSA through endothelial dysfunction caused by these mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Low Glomerular Filtration Rate Is Associated With High Prevalence of Vasospastic Angina

Koga

Ikeda

Nakata

et al. 2011

Circ J

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“…Endothelial dysfunction is a key process in atherosclerosis, which independently predicts CVD events (24) ; and it becomes progressively more common as renal function declines (25) . However, studies of supplementation with either 5 mg/d folic acid or 5 mg/d folic acid combined with 4 g/d betaine for 12 weeks, followed by either 1 or 5 mg/d folic acid for 40 weeks showed no improvement of endothelial function in patients on peritoneal dialysis or HD (26,27) .…”

Section: Studymentioning

confidence: 99%

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

et al. 2012

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The efficacy of homocysteine (Hcy)-lowering therapy in reducing the risk of CVD among patients with chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to determine whether pooling the data from the few small randomised, controlled trials that address this topic would improve the statistical power of the analysis and resolve some of the inconsistencies in the results. Randomised, controlled clinical trials (RCT) were identified from MEDLINE, EMBASE, www.clinicaltrials.gov, the Cochrane Controlled Clinical Trials Register Database and Nephrology Filters. Independent extraction of articles was performed using predefined data fields. The primary outcome was relative risk (RR) of CVD, CHD, stroke and all-cause mortality for the pooled trials. A stratified analysis was planned, assessing the RR for cardiovascular events between the patients on and not on dialysis. Overall, ten studies met the inclusion criteria. The estimated RR were not significantly different for any outcomes, including CHD (RR 1·00, 95 % CI 0·75, 1·31, P ¼ 0·97), CVD (RR 0·94, 95 % CI 0·84, 1·05, P ¼ 0·30), stroke (RR 0·83, 95 % CI 0·57, 1·19, P ¼ 0·31) and all-cause mortality (RR 1·00, 95 % CI 0·92, 1·09, P ¼ 0·98). In the stratified analysis, the estimated RR were not significantly different for cardiovascular events regardless of dialysis or in combination with vitamin B therapy or the degree of reduction in Hcy levels. Our meta-analysis of RCT supports the conclusion that Hcy-lowering therapy was not associated with a significant decrease in the risk for CVD events, stroke and all-cause mortality among patients with CKD.Key words: CVD: Chronic kidney disease: Folic acid: Homocysteine-lowering therapy: Homocysteine: Meta-analyses CVD is the leading cause of mortality both among the general population and among patients with chronic kidney disease (CKD). The rate of mortality from CVD among patients on haemodialysis (HD) is 20-fold higher than that among the general population (1) , and impaired renal function per se is a very strong cardiovascular prognostic factor (2,3) . Therefore, much attention has been focused on managing risk factors to attempt to reduce the associated CVD risks, especially among patients with CKD. Elevated plasma total homocysteine (Hcy) has been proposed as a risk factor for cardiovascular morbidity and mortality in patients either with normal renal function or with CKD (4,5) . Among patients with CKD, plasma Hcy levels tend to increase with decreasing glomerular filtration rate (6) ; thus, hyperhomocysteinaemia may potentially further increase the risk of CVD in this special population. In the Cardiovascular Risk Extended Evaluation in Dialysis trial, investigators followed-up on 175 patients with kidney failure for 29 months and found that an increase in Hcy of 10 mmol/l was associated with a 20 % increased risk for CVD events (7) . In another study, Hcy was found to be a strong independent predictor of mortality among patients on HD with a 3 % increase in mortality for each 1 mmol...

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Role of Nitric Oxide–Producing and–Degrading Pathways in Coronary Endothelial Dysfunction in Chronic Kidney Disease

Cited by 70 publications

References 47 publications

High dietary protein intake induces endothelial dysfunction in uninephrectomized rats

High dietary protein intake induces endothelial dysfunction in uninephrectomized rats

Low Glomerular Filtration Rate Is Associated With High Prevalence of Vasospastic Angina

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

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