Renal synthesis of arginine in chronic renal failure: In vivo and in vitro studies in rats with 5/6 nephrectomy

Bouby, Nadine; Hassler, Christine; Parvy, P; Bankir, Lise

doi:10.1038/ki.1993.300

Cited by 48 publications

(39 citation statements)

References 24 publications

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“…Surprisingly, however, there is little or no decrease in plasma arginine in these patients. The basis for the maintenance of plasma arginine at normal or near-normal levels is unknown, but probably involves a combination of factors [40,122], including increased release of arginine by protein catabolism in skeletal muscle, increased arginine synthesis at extrarenal sites, hypertrophy of proximal tubules, hyperfiltration (which increases the amount of citrulline filtered per nephron), and an increased rate of arginine synthesis due to elevated plasma levels of citrulline. The last point follows from the finding that rates of renal arginine synthesis are essentially a function of plasma citrulline levels [50].…”

Section: Renal Arginine Synthesismentioning

confidence: 99%

Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,389

2,036

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Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified

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Section: Renal Arginine Synthesismentioning

confidence: 99%

Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,389

2,036

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“…23 Alternatively, impaired NO production may also have resulted from accumulation of the endogenous NOS-inhibitor ADMA in patients with end-stage renal disease, which is well documented. [7][8][9] Furthermore, the bioavailability of the NOS substrate L-arginine has been found to be decreased in subtotally nephrectomized rats 10,11 as well as in dialysis patients, possibly as a result of malnutrition or arginine loss caused by hemodialysis. 12 In the present study, plasma L-arginine levels of the CRF patients also tended to be lower than that of the other groups, although the differences were not significant.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Production Is Reduced in Patients With Chronic Renal Failure

Wever

Boer

Hijmering

et al. 1999

ATVB

197

117

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Abstract-In patients with chronic renal failure (CRF), atherosclerosis is a major cause of cardiovascular morbidity and mortality. Generally, atherosclerosis has been associated with a reduced bioavailability of nitric oxide (NO). Experimental studies have indicated the presence of enhanced NO degradation by reactive oxygen species as well as decreased NO production as possible causes for this reduced NO bioavailability. So far, the question whether or not NO production is impaired in patients with CRF has never been investigated. 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 dysfunction of NO synthase (NOS), we compared the NO production of these patients to that of 2 other groups known to have endothelial dysfunction, ie, 7 patients with familial hypercholesterolemia (FH) who did not yet have signs of clinical cardiovascular disease (all nonsmokers), and 5 cigarette smokers. These groups were also compared with 7 nonsmoking, age-matched healthy subjects. Whole body NO production, determined as in vivo arginine-to-citrulline conversion, was assessed by giving an intravenous infusion of [ 15 N 2 ]-arginine as a substrate for NOS and measuring isotopic plasma enrichment of [15 N]-citrulline by LC-MS. NO production in the CRF patients (0.13Ϯ0.02 mol ⅐ kg -1 ⅐ h -1 ) was significantly lower (PϽ0.05) than in the corresponding control group (0.23Ϯ0.09 mol ⅐ kg -1 ⅐ h -1 ). NO production also tended to be lower in the FH patients (0.16Ϯ0.04 mol ⅐ kg -1 ⅐ h -1 ), but the difference with the corresponding control group did not reach significance (0.22Ϯ0.06 mol ⅐ kg -1 ⅐ h -1 ). In the group of smokers, NO production was similar to that in nonsmokers (0.22Ϯ0.09 mol ⅐ kg -1 ⅐ 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 in these patients should be primarily directed toward improvement of NO production. The finding of only a tendency toward reduction of NO production in patients with FH and the absence of a reduction in cigarette smokers suggests that other mechanisms such as enhanced NO degradation may be involved in the decrease of NO bioavailability in these groups. (Arterioscler Thromb Vasc Biol. 1999;19:1168-1172.) Key Words: nitric oxide Ⅲ chronic renal failure Ⅲ atherosclerosis Ⅲ endothelium Ⅲ hypercholesterolemia P remature atherosclerosis is one of the primary causes of morbidity and mortality in patients with chronic renal insufficiency. 1 Over the last decade endothelial dysfunction has been identified as an early mediator in this process. Nitric oxide (NO) is one of the main factors involved in the antiatherosclerotic effects of the endothelium, 2 and chronic renal failure (CRF) has been associated with impaired NO bioavailability in the absence of concomitant risk factors, [3][4][5] even in children. 6,7 However, the finding of a reduced NO bioavailabi...

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“…It has also been Biochemistry Section suggested that in renal failure, an NO deficiency could result from a reduced arginine availability, since the kidney is a major site of an endogenous arginine synthesis [5,6]. However, a recent study which was done by Boudy et al, showed that the renal arginine synthesis and the arginine plasma levels were not diminished in the remnant kidneys, despite a significant reduction in the GFR [7]. Based on this, it is unlikely that the substrate supply of arginine would be rate limiting for the Nitric Oxide Synthases (NOS), even with the severe reduction of the functional renal mass, unless there are extraordinary arginine demands (i.e., sepsis or vigorous cytokine-induced NOS activation, as in dialysis).…”

Section: Introductionmentioning

confidence: 96%