Hypovitaminosis D is associated with endothelial dysfunction in patients with non-dialysis chronic kidney disease.

OBJECTIVE: Cardiovascular events are highly prevalent in chronic kidney disease (CKD). Hypovitaminosis D and vascular endothelial dysfunction are risk factors for cardiovascular morbidity and mortality and they both are common in CKD patients. This study aimed to investigate the association between hypovitaminosis D and endothelial dysfunction in non-dialysis CKD patients. METHODS: In 117 non-dialysis CKD patients, we assessed endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin. 25-hydroxyvitamin D [25(OH)D] was measured by electrochemiluminescence immunoassay. RESULTS: Brachial artery FMD was lower in vitamin D-deficient and -insufficient versus vitamin D-sufficient groups, with the lowest value observed in the vitamin D-deficient group. Conversely, sVCAM-1 and sE-selectin were higher in vitamin D-deficient and -insufficient groups versus vitamin D-sufficient, and the highest value was observed in the vitamin D-deficient group. There was a positive association between FMD and 25(OH)D (r = 0.556, p < 0.001) and negative correlations between both sVCAM-1 (r = -0.549, p < 0.001) and sE-selectin (r = -0.360, p < 0.001) and 25(OH)D. These associations remained significant after adjusting for confounders. CONCLUSIONS: Hypovitaminosis D is associated with endothelial dysfunction in non-dialysis CKD patients. Further studies are needed to confirm whether vitamin D supplementation can improve endothelial function and reduce cardiovascular events in these patients.

Fosinopril and losartan regulate klotho gene and nicotinamide adenine dinucleotide phosphate oxidase expression in kidneys of spontaneously hypertensive rats.

BACKGROUND/AIMS: Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosinopril (Fos) and losartan (Los) on Klotho and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in kidneys of spontaneously hypertensive rats (SHR). METHODS: Twenty-four male 22-week-old SHR were randomly divided into three groups: model group, Fos group and Los group. Wistar-Kyoto rats were taken as control. After 8 weeks, urinary N-acetyl-ß-D-glucosaminidase (NAGase), 24 h urinary protein (Upro), serum creatinine (Scr), blood urea nitrogen (BUN) and renal pathological changes were detected. Renal mRNA and protein expression of Klotho and three subunits of NADPH oxidase protein expression were evaluated. RESULTS: As compared to the model group, NAGase, Upro, Scr and BUN were decreased; the typical renal pathological damage was relieved in the Fos or Los group. Fos or Los inhibited the reduction of Klotho expression, and reduced the elevation of NADPH oxidase expression. CONCLUSION: Abnormal expression of Klotho and NADPH oxidase plays important roles in progression of hypertensive renal damage. Fos and Los can increase Klotho expression, and inhibit NADPH oxidase expression, which may be one of the mechanisms of their protective effects in hypertensive renal damage.

[Effect of spironolactone on the expression of Toll-like receptor 4 in renal tubular epithelia cells exposed to high glucose].

OBJECTIVE: To study the expression of Toll-like receptor 4 (TLR4) in renal tubular epithelial cells exposed to high glucose and the effect of spironolactone on the TLR4 expression. METHODS: In vitro renal tubular epithelial cells (NRK-52E) were randomly exposed to DMEM culture solution with low glucose (5 mmol /L), high glucose (25 mmol/L) or 10(-7) mol/L spironolactone plus 25 mmol/L glucose. Immunohistochemistry, RT-PCR and Western blot were used to determine TLR4 protein and mRNA expression. The levels of IL-6 and TNF-alpha in the cell culture supernatant were determined using ELISA. RESULTS: The expression of TLR4 mRNA in the high glucose group began to increase 6 hrs and remained at a higher level up to 24 hrs after exposure as compared with the low glucose group. The TLR4 mRNA expression in the spironolactone treatment group was significantly lower than that in the high glucose group, although it was higher than that in the low glucose group between 6 and 24 hrs after exposure. TLR4 protein expression increased significantly in the high glucose group 24 and 48 hrs after exposure compared with that in the low glucose group. The TLR4 protein expression in the spironolactone treatment group was lower than that in the high glucose group, but higher than that in the low glucose group. IL-6 and TNF-alpha expression in the supernatant from the NRK-52E cells in the high glucose groups increased significantly as compared with the low glucose group. The spironolactone treatment group had significantly reduced IL-6 and TNF-alpha expression compared with the high glucose group. CONCLUSIONS: High glucose triggers an increase in the expression of TLR4 and inflammatory factors in NRK-52E cells. TLR4 may participate in the progress of diabetic nephropathy. Spironolactone can reduce expression of TLR4 and inflammatory factors, which might be attributed to one of the mechanisms of protection by spironolactone against diabetic nephropathy.

[Effects of fosinopril and losartan on the expression of Toll- like receptor 4 in renal tubular epithelia cells].

OBJECTIVE: To determine the mechanism of Toll-like receptor 4(TLR4) in hypertensive renal injury and the protective effect of fosinopril(Fos) and losartan(Los). METHODS: NRK-52E was incubated into 5 groups: NRK-52E (normal control), NRK-52E+AngII, NRK-52E+AngII+Fos(10(-5) mmol/L),and NRK-52E+AngII+Los(10(-5) mmol/L), NRK-52E +AngII+Fos(10(-5) mmol/L)+Los(10(-5) mmol/L). TLR4-specific RNAi plasmids were stably transfected into NRK-52E. After 24 h, TLR4, IL-6, and TNF-alpha mRNAs were examined by reverse transcription-polymerase chain reaction(RT-PCR). TLR4 proteins were detected by Western blot, NF-kappaB nuclear translocations were tested by immunocytochemistry,and IL-6 and TNF-alpha supernatant levels were tested by enzyme linked immuno-sorbent assay(ELISA). RESULTS: TLR4, NF-kappaB, IL-6,and TNF-alpha were highly expressed in AngII induced NRK-52E(P<0.01). In NRK-52E that was stably transfected TLR4-special RNAi plamids, TLR4 protein and mRNA expression were obviously inhibited(P<0.05). After stimulation by AngII, the TLR4, IL-6, TNF-alpha levels in the stabe transfection group were increased compared with the normal group(P<0.05). Fos or/and Los down-regulated TLR4, IL-6, and TNF-alpha expressions(P<0.05), but no cooperation was observed. CONCLUSION: TLR4 may lead to inflammatory reaction in hypertensive renal injury. Fos or/and Los can decrease the expressions of TLR4 and correlate inflammatory factors, which may be part of the renal protective mechanism.

[Effect of bizhongxiao decotion on TNF-alpha and interleukin-1beta in plasma of rats with C II-induced rheumatoid arthritis].

OBJECTIVE: To observe the influence of bizhongxiao decotion (BZXD) on the plasma TNF-alpha and IL-1beta in rats with C II-induced arthritis (CIA) and to explore the mechanism of BZXD in the treatment of rheumatoid arthritis. METHODS: We divided 75 rats into 4 groups randomly. The rat experimented arthritis model was established by subcutaneous injection with collagen II. The plasma TNF-alpha and IL-1beta levels were detected with the radio-immunity assay at different time spots. RESULTS: The incidence of arthritis in the rats immunized with C II was approximately 88%. The plasma TNF-alpha and IL-1beta levels of the model group, BZXD group and methotrexate (MTX) group were notably higher than those of the normal group (P < 0.05). The plasma TNF-alpha and IL-1beta levels of the model group were higher than those of the MTX control group and BZXD treatment group at different time spots (P < 0. 01). The plasma TNF-alpha and IL-1beta levels rose step by step, but those of the BZXD group and MTX group decreased gradually. Moreover, the plasma TNF-alpha and IL-1beta levels of the rats of BZXD group were lower than those of the MTX group (P < 0. 05). CONCLUSION: TNF-alpha and IL-1beta play a very important role in the formation and development of rheumatoid arthritis. Both BZXD and MTX can notably decrease the plasma TNF-alpha and IL-1beta levels, but the effect of BZXD is better than that of MTX.