Nitric oxide production is reduced in patients with chronic renal failure

In patients with chronic renal failure (CRF), atherosclerosis is a major ca use of cardiovascular morbidity and mortality. Generally, atherosclerosis h as been associated with a reduced bioavailability of nitric oxide (NO). Exp erimental studies have indicated the presence of enhanced NO degradation by reactive oxygen species as well as decreased NO production as possible cau ses for this reduced NO bioavailability. So far, the question whether or no t NO production is impaired in patients with CRF has never been investigate d. Therefore, we measured whole body NO production in 7 patients with CRF, and in 7 matched healthy subjects. To assess the relative importance of a d ysfunction of NO synthase (NOS), we compared the NO production of these pat ients to that of 2 other groups known to have endothelial dysfunction, ie, 7 patients with familial hypercholesterolemia (FH) who did not yet have sig ns of clinical cardiovascular disease (all nonsmokers), and 5 cigarette smo kers. These groups were also compared with 7 nonsmoking, age-matched health y subjects. Whole body NO production, determined as in vivo arginine-to-cit rulline conversion, was assessed by giving an intravenous infusion of [N-15 (2)]-arginine as a substrate for NOS and measuring isotopic plasma enrichme nt of [N-15]-citrulline by LC-MS. NO production in the CRF patients (0.13+/ -0.02 mu mol . kg(-1) . h(-1)) was significantly lower (P<0.05) than in the corresponding control group (0.23+/-0.09 mu mol . kg(-1) . h(-1)). NO prod uction also tended to be lower in the FH patients (0.16+/-0.04 mu mol . kg( -1) . h(-1)), but the difference with the corresponding control group did n ot reach significance (0.22+/-0.06 mu mol . kg(-1) . h(-1)). In the group o f smokers, NO production was similar to that in nonsmokers (0.22+/-0.09 mu mol . kg(-1) . h(-1)). In conclusion, it is demonstrated for the first time that basal whole body NO production is reduced in patients with CRF. This finding implies that therapeutic interventions to endothelial dysfunction i n these patients should be primarily directed toward improvement of NO prod uction. The finding of only a tendency toward reduction of NO production in patients with FH and the absence of a reduction in cigarette smokers sugge sts that other mechanisms such as enhanced NO degradation may be involved i n the decrease of NO bioavailability in these groups.