Impaired resistance artery function in patients with end-stage renal disease.
ABSTRACT We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈ 200 μm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls. NO (nitric oxide) contribution to flow was lacking in ESRD patients, but present in the controls. ADMA (asymmetrical dimethyl L-arginine) levels were higher in the ESRD group compared with the control group. Dilatation in response to acetylcholine was reduced in ESRD patients compared with controls, but response to NO donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased in arteries from ESRD patients compared with controls. Arterial remodelling was absent in ESRD patients. There was no difference between the groups in myogenic tone, vascular reactivity or sensitivity to several vasoconstrictors. Arterial distensibility, reflecting passive properties of the vascular wall, was reduced in ESRD patients compared with controls. Exclusion of ESRD patients with diabetes and/or cardiovascular disease from analyses had no influence on the main findings. Thus we propose that uraemia has a strong impact on endothelial function and passive properties of the arterial wall of human peripheral resistance vasculature. The reduced contribution of NO to flow stimulus via enhanced nitrosative stress and higher plasma concentrations of ADMA may suggest potential mechanisms behind endothelial dysfunction in the resistance peripheral circulation in ESRD.
- [show abstract] [hide abstract]
ABSTRACT: Analytical and immunological methodologies and occasionally both methodologies have been applied to detect and quantify 3-nitrotyrosine in almost every major organ system. In certain diseases increased levels of 3-nitrotyrosine have been correlated with elevated levels of other indices of oxidative stress. Numerous reports have established that nitration is a biological process derived from the biochemical interaction of nitric oxide or nitric oxide-derived secondary products with reactive oxygen species. This article addresses critical issues regarding this biological process, namely the biochemical pathways for nitration of tyrosine residues in vivo, potential protein targets, and pathophysiological consequences of protein tyrosine nitration.Archives of Biochemistry and Biophysics 09/1998; 356(1):1-11. · 3.37 Impact Factor
- Clinical Science 06/1999; 96(5):439-40. · 4.86 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The purpose of this study was to examine the glycoxidation and lipoperoxidation products in the collagen of the myocardium in hemodialysis (HD) patients and age-matched control subjects. Cardiac samples from 15 autopsied subjects (HD, n=6; control, n=9) were sequentially extracted with 0.9% NaCl and collagenase to obtain two fractions [soluble fraction (SF) and collagenase soluble fraction (CSF)]. The glycoxidation and lipoperoxidation products of these two fractions were measured by pentosidine-linked fluorescence (lambda(ex), 335; lambda(em), 385) and malondialdehyde (MDA)-linked fluorescence (lambda(ex), 390; lambda(em), 460), respectively. Both pentosidine- and MDA-linked fluorescence were found to have significantly increased more in the collagenase soluble fraction (CSF) extracted form the anterior and posterior wall in HD patients than in the controls (P<0. 05, control, n=9 vs. HD, n=6). Interestingly, the level of the lipid peroxides strongly correlated with that of the glycoxidation product in CSF (both P<0.0001 for the anterior and posterior wall). In contrast, in SF, which did not contain matrix collagen, neither significant difference nor correlation in the levels of pentosidine- and MDA-linked fluorescence was observed in these two groups. the present study provides the first biochemical evidence for an increase in glycoxidation and a close link between glycoxidation and lipoperoxidation in the collagen of the myocardium in hemodialysis patients. These findings suggest that these two spontaneous chemical reactions in the collagen matrix of myocardium may synergistically contribute to cardiac damage in hemodialysis patients.Cardiovascular Research 08/2000; 47(2):306-13. · 5.94 Impact Factor