Effect of experimental chronic renal failure upon the production of urea, as measured by the liver arginase activity in rats

Silva, A. da Costa e; Albuquerque, Zuleica Portela

doi:10.1007/bf01932356

“…Therefore in endothelial cells arginine plays a pivotal role in two enzyme pathways, namely the NO pathway and arginase pathway. The arginase pathway has not been studied in uraemic endothelial cells, but hepatocytes of uraemic rats, and also erythrocytes and leucocytes from uraemic patients, all show reduced arginase activity [27,28]. Should similar changes occur in uraemic endothelial cells, there would be increased availability of L-arginine to be utilized by NOS which could result in increased NO production.…”

Section: Scheme 1 Inhibition Of Arginase By Uraemia Results In Increamentioning

confidence: 98%

“…Ornithine concentrations in supernatants and cells were both significantly lower in the unstimulated uraemic groups, which implies reduced arginase activity. Reduced arginase activity has been demonstrated in hepatocytes from uraemic rats [27], and also in erythrocytes and leucocytes from patients with chronic renal failure [28]. There is also evidence to suggest inverse regulation of arginase activity by the NO pathway.…”

Section: Discussionmentioning

confidence: 96%

Altered l-arginine metabolism results in increased nitric oxide release from uraemic endothelial cells

THURAISINGHAM¹,

ROBERTS²,

WILKES³

et al. 2002

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A B S T R A C TResults regarding the nitric oxide (NO) system in uraemia are contradictory. L-Arginine, the precursor of NO, is also metabolized by arginase to form ornithine and urea. In the present study, endothelial NO production and arginine metabolism in uraemia were assessed. In addition an in vivo model was used to examine excess consumption of NO in uraemia. NO and amino acid measurements were made from basal and stimulated (by bradykinin) uraemic and control endothelial cells. Reverse-transcriptase PCR was used to assess endothelial NO synthase (eNOS) and inducible NOS (iNOS) expression. Finally, aortae of uraemic rats were stained for nitrotyrosine (a marker of peroxynitrite). Basal uraemic cells produced more NO than the control cells. L-Arginine levels were greater in uraemic (supernatants/cells), but ornithine levels were higher in control (supernatants/cells). Following stimulation, NO levels in supernatants were similar, but the rise in NO production was greater in control compared with uraemic cells; L-arginine levels still remained higher in uraemic supernatants/cells. Differences in ornithine concentration (supernatants/cells) disappeared following bradykinin stimulation, due to a rise in ornithine levels in the uraemic group. There was no difference in eNOS expression, nor was iNOS detected in either group. Only aortae from uraemic rats showed evidence for nitrotyrosine staining. These studies demonstrated increased basal NO release in uraemic endothelial cells, perhaps by inhibition of arginase and hence diversion of arginine to the NO pathway. The increased NO produced under basal conditions may be inactive due to excessive consumption, resulting in peroxynitrite formation. Interestingly, bradykinin appears to restore arginase activity in uraemia, resulting in normalization of NO production.

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“…Reduced arginase activity has been demonstrated in hepatocytes from uraemic rats [27], and also in erythrocytes and leucocytes from patients with chronic renal failure [28]. Ornithine concentrations in supernatants and cells were both significantly lower in the unstimulated uraemic groups, which implies reduced arginase activity.…”

Section: Discussionmentioning

confidence: 97%

Altered l-arginine metabolism results in increased nitric oxide release from uraemic endothelial cells

Thuraisingham

¹

,

Roberts

²

,

Wilkes

³

et al. 2002

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A B S T R A C TResults regarding the nitric oxide (NO) system in uraemia are contradictory. L-Arginine, the precursor of NO, is also metabolized by arginase to form ornithine and urea. In the present study, endothelial NO production and arginine metabolism in uraemia were assessed. In addition an in vivo model was used to examine excess consumption of NO in uraemia. NO and amino acid measurements were made from basal and stimulated (by bradykinin) uraemic and control endothelial cells. Reverse-transcriptase PCR was used to assess endothelial NO synthase (eNOS) and inducible NOS (iNOS) expression. Finally, aortae of uraemic rats were stained for nitrotyrosine (a marker of peroxynitrite). Basal uraemic cells produced more NO than the control cells. L-Arginine levels were greater in uraemic (supernatants/cells), but ornithine levels were higher in control (supernatants/cells). Following stimulation, NO levels in supernatants were similar, but the rise in NO production was greater in control compared with uraemic cells; L-arginine levels still remained higher in uraemic supernatants/cells. Differences in ornithine concentration (supernatants/cells) disappeared following bradykinin stimulation, due to a rise in ornithine levels in the uraemic group. There was no difference in eNOS expression, nor was iNOS detected in either group. Only aortae from uraemic rats showed evidence for nitrotyrosine staining. These studies demonstrated increased basal NO release in uraemic endothelial cells, perhaps by inhibition of arginase and hence diversion of arginine to the NO pathway. The increased NO produced under basal conditions may be inactive due to excessive consumption, resulting in peroxynitrite formation. Interestingly, bradykinin appears to restore arginase activity in uraemia, resulting in normalization of NO production.

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Determinants of ureagenesis, with particular reference to renal failure

Walser¹

1980

Kidney International

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Effect of experimental chronic renal failure upon the production of urea, as measured by the liver arginase activity in rats

Abstract: A significant diminution in liver arginase activity of chronic renal failure uremic rats is described, thus implying that the experimental finding of an increased urea production is not due to a depressed arginase activity.

Cited by 4 publications

References 13 publications

Altered l-arginine metabolism results in increased nitric oxide release from uraemic endothelial cells

Altered l-arginine metabolism results in increased nitric oxide release from uraemic endothelial cells

Altered l-arginine metabolism results in increased nitric oxide release from uraemic endothelial cells

Determinants of ureagenesis, with particular reference to renal failure

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