state of plasma nitric oxide metabolites [NO-2 and NO-3] and endothelin-1 in patients with chronic renal failure and/or ischemic heart disease

ABSTRACT

the present study was designed to evaluate the endothelium potential vasodilatation and vasoconstriction major factors in groups of patients with CRF or IHD singly or combined. Patients and Cases eligible for inclusion in the present study were those with CRF solely [30 patients], IHD singly [15 patients] or combination of CRF with IHD simultaneously [15 patients]. The included controls [15 cases] were clinically healthy subjects who were highly matched to cases for age, gender and body weight. The designed biochemical analyses included Plasma endothelin- 1 [ET-1] using enzyme immunometric assay [EIA] and plasma nitric oxide metabolites [NO[-2]/NO[-3] by photometric assay. The median plasma NO[-2] concentrations among single CRF, single IHD or combined CRF with IHD were not significantly different from those observed in controls. Alternatively the median concentration of plasma total NO[-3]] [NO[x]] and the ratio of NO[-3] to NO[-2] among CRF with or without IHD groups were significantly higher than controls. With regard plasma NO[x], its median concentration in IHD patients showed no significant difference from controls, but there was a significant decrease compared with single CRF or combined CRF with IHD. At the same time, statistically significant differences in the median plasma concentrations of ET- 1 between cases allocated in the three different diseased groups and control group were observed. Moreover, statistically significant higher median plasma concentrations of NO[x] and lower ET- 1 were noted in noncardiac CRF cases as compared with the nonuremic IHD patients. There was a positive relation between the plasma concentrations of NO[-2] and NO[x] in all, -studied groups and between plasma concentrations of NO[x] and ET- 1 in CRF patients whether single or combined with IHD. High ET- 1 and NO[x] levels were found in patients with advanced chronic renal failure with or without IHD, a feature that was not noted in uncomplicated IHD. Whether plasma NO[x] concentrations necessarily reflect production of the hemodynamically active component, NO is not yet settled. Therefore, plasma NOx levels, even when obtained under conditions of dietary NO[x] control, do not give stand-alone information about NO production, particularly when renal function is impaired. Although definitive proof that ET- 1 as a primary inducer of atherosclerosis is still elusive, it is likely that ET- 1- is at least an important contributor to the atherogenic process. Vascular endothelial cells in atherosclerosis may synthesize greater quantities of nitric oxide than nondiseased cells, but it is rapidly inactivated by oxidative reaction or converted to the toxic peroxynitrite