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Background: Hemodialysis patients (HD) are exposed to oxidative stress which contributes to cardiovascular disease and accelerated atherosclerosis, major causes of mortality in these patients. A new dialysis membrane coated with vitamin E has been proposed against oxidative stress and atherosclerosis due to their ability to inhibit lipid peroxidation by interacting with scavengers. The mechanisms however are not completely clarified. This study evaluated, using a molecular biology approach, the effect of 6 months treatment with vitamin E-modified dialyzers, CL-E, on the gene expression of oxidative stress related proteins and markers., Patients and Methods: To this end, the gene expression of p22phox, a NAD(P)H oxidase subunit closely linked with the generation of superoxide anions and of Heme oxygenase-1 (HO-1), induced by and protective from oxidative stress, were evaluated by RT-PCR in mononuclear cells from 5 patients under 3 times a week chronic bicarbonate dialysis. Hydroperoxide (HPO) and total antioxidant power (AOP) plasma levels were evaluated at 3 and 6 months of treatment. HPO was also evaluated in 8 patients under CL-E treatment for 1 year and compared with 8 patients treated with cuprammonium-ryon filter (TAF)., Results: p22phox mRNA decreased from 0.61 +/- 0.05 d.u. to 0.48 +/- 0.03, p < 0.01 while HO-1 increased from 0.55 +/- 0.04 d.u. to 0.62 +/- 0.03, p < 0.01. HPO decreased in CL-E treated patients: from 2.72 +/- 0.26 microM to 1.45 +/- 0.27 at 3 months (p < 0.001) to 0.87 +/- 0.11, p < 0.001 at 6 months, while AOP increased: from 752 +/- 90 mmol/L to 1057 +/- 105, p < 0.001 at 6 months. HPO was also reduced in 1 year Excebrane CL-E treated patients compared with cuprammonium treated patients: 2.25 +/- 0.3 vs. 1.42 +/- 0.11 microM, p < 0.001., Conclusion: The reduced expression of oxidative stress related proteins and markers gives further support to the efficacy of the use of Vitamin E coated dialysers for the prevention or slowing progression of cardiovascular disease and atherosclerosis, major complications and causes of mortality in these patients in which oxidative stress plays a pivotal role.

Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to TGFbeta production, NO degradation, endothelial dysfunction, hypertension and post-transplant nephropathy. Carvedilol, alpha1-beta-blocker with strong antioxidant activity, may interfere with this chain of events. Therefore, we measured monocyte ecNOS, TGFbeta and heme oxygenase-1 (HO-1) mRNA level and plasma nitrite/nitrate, 3-nitrotyrosine, an estimate of peroxynitrite, and total plasma antioxidant power in kidney-transplanted patients with post-transplant hypertension, before and after treatment with carvedilol, 25 - 50 mg o.d. orally for 4 months (n = 15). The dihydropyridine calcium channel blocker nifedipine (n = 10) was used as comparator antihypertensive drug. Blood pressure fell to a similar extent with both drugs. Carvedilol increased plasma antioxidant power and HO-1 mRNA and reduced 3-nitrotyrosine and TGFbeta mRNA levels, while the same was not observed with nifedipine. Monocyte ec NOS mRNA levels and plasma nitrite/nitrate were higher in the patients than in a normotensive healthy control group and were unaffected by either treatment. In conclusion, carvedilol reduces the oxidative stress and corrects the altered cellular signaling mediated by oxidative stress in CsA-induced post-transplant hypertension. Therefore, it may prevent long-term complications, such as endothelial dysfunction, fibrogenesis and post-transplant nephropathy by decreasing NO degradation and production of TGFbeta, a key fibrogenic cytokine, and by activating HO-1 production.

Aim: Patients with Bartter's syndrome and Gitelman's syndrome have reduced vascular reactivity, normo-hypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension. Since we found that both types of patients have increased urinary NO2-/NO3-, metabolites of NO, that correlated with their increased urinary cGMP, second messenger of NO, we examined the possible role of NO system in the pathophysiology of these syndromes., Patients and Methods: We used a molecular biologic approach and studied ecNOS gene expression by PCR-amplification of cDNA obtained by RT-PCR of RNA extracted by patients and healthy controls monocytes., Results: ecNOS is overexpressed in monocytes from patients with Bartter's and Gitelman's syndrome relative to controls: - 0.306 +/- 0.012 Densitometric Units (0.313 +/- 0.006, N = 3 for Bartter's patients; 0.302 +/- 0.009, N = 5 for Gitelman's patients) vs. 0.192 +/- 0.018, p < 0.0001., Conclusion: This overexperession presumably accounts for their increased NO production; thus it could be likely that elevated ecNOS and NO levels are a part of pathophysiological process(es) that leads to their characteristic reduced vascular responses. However, the relationship between the alterations in the NO signalling system observed in this study and the mutations in either Na+-K+-2Cl cotransporter or in a K+ channel ROMK or in Cl- channel ClCNKB in Bartter's syndrome and in Na+-Cl- cotranstransporter in Gitelman's syndrome, recently reported as their primary defects remains to be defined.