[Vascular damage in chronic renal failure. The increase of vascular nitrotyrosine and cytochines accumulation is accompanied by an increase of endothelial nitric oxide synthase (eNOS) expression].
Patients with chronic renal failure (CRF) are at a greatly increased risk of cardiovascular mortality. This fact could be due to the presence of conventional risk factor and specific uremic as increase of oxidative stress, hyperhomocystaenemia, deranged calcium-phosphate metabolism and chronic inflammatory state. In order to analyze the vascular effects of CRF, we studied the histomorphometric characteristics (intima-media thickness and monocyte chemoattractant protein (MCP-1) accumulation (inmunohistochemical) on radial artery from 13 patients with CRF. We determined by Western blot analysis, the vascular nitrotyrosin abundance (footprint of nitric oxide (NO) inactivation by reactive oxygen species (ROS), and the endothelial nitric oxide synthase (eNOS) expression. The NOS activity was, also, determined. The results were compared with those obtained in pudenda artery from a healthy control group (n: 16). The CRF group showed a significant increase in intima and media thickness 108 +/- 16 vs 14 +/- 2.5 microm, p < 0.001 and 291 +/- 19 vs 153 +/- 15 microm, p < 0.001, respectively). The CRF group exhibited a marked elevation of MCP-1 vascular expression (2 +/- 0.15 vs 0.6 +/- 0.12 u, p < 0.001). A significant positive correlation was found between MCP-1 vascular expression and its inmunohistochemical deposits (r: 0.98, p < 0.0001). Nitrotyrosin abundance (western blot) was significantly increased in artery of CRF patients (2.1 +/- 0.1 vs 0.42 +/- 0.1 u, p < 0.0001). No significant differences was found in NOS activity between CRF and control groups. However, eNOS expression was greatly increased in the CRF patients (1.73 +/- 0.1 vs 0.67 +/- 0.1 u, p < 0.001). A significant positive correlation was found between nitrotyrosin and eNOS expression and systolic arterial pressure. However, the differences between CRF and control groups persisted after statistically fitting to arterial pressure. The present study demonstrate that in CRF there are arterial preatherosclerotic changes and an increase of vascular nitrotyrosin accumulation, which is the footprint of NO inactivation by ROS. The secondary NO inactivation can, in turn, contribute to eNOS vascular upregulation.
Gómez-Fernández
P
P
Servicio Nefrología Hospital de Jerez, Cádiz.
Pérez-Requena
J
J
Sánchez-Margalet
V
V
Esteban
J
J
Murillo-Carretero
M
M
Almaraz-Jiménez
M
M
D001808:Blood Vessels / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004727:Endothelium / Q000201:enzymology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology* / Q000378:metabolism*
D016207:Cytokines; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase