L-Arginine deficiency and supplementation in experimental acute renal failure and in human kidney transplantation

Schramm, Lothar; La, Mylinh; Heidbreder, E.; Hecker, Markus; Beckman, Joe S.; Lopau, Kai; Zimmermann, Josef; Rendl, J.; Reiners, Christoph; Winderl, Sabine; Wanner, Christoph; Schmidt, Harald

doi:10.1046/j.1523-1755.2002.00268.x

Cited by 78 publications

(69 citation statements)

References 40 publications

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“…NOS substrate supplementation has beneficial effects on both blood pressure and renal disease in clinical trials (35,47,52) and in experimental models (12,14,27,32,40,42,50). In animals with ureteral obstruction, the administration of L-arginine increases GFR and renal blood flow to the postobstructed kidney and decreases the infiltration of macrophages of the renal parenchyma (29).…”

Section: Discussionmentioning

confidence: 99%

“…Reduced levels of L-arginine have been observed in renal failure, but the clinical relevance is uncertain, as the measured serum concentrations are well in excess of the K m for eNOS (1,38). Nevertheless, both clinical (20,47,52,60) and experimental studies (12,14,18,22,23,36,44) have demonstrated that substrate supplementation stimulates NO production and attenuates renal damage and salt-sensitive hypertension. Furthermore, chronic NO inhibition with N G -nitro-Larginine methyl ester (L-NAME), an antagonist for L-arginine, causes salt-sensitive hypertension and the development of renal injury (62).…”

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confidence: 99%

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Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals

Carlström¹,

Brown²,

Edlund³

et al. 2008

American Journal of Physiology-Renal Physiology

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Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals. Am J Physiol Renal Physiol 294: F362-F370, 2008. First published November 21, 2007 doi:10.1152/ajprenal.00410.2007.-Hydronephrotic animals develop renal injury and hypertension, which is associated with an abnormal tubuloglomerular feedback (TGF). The TGF sensitivity is coupled to nitric oxide (NO) in the macula densa. The involvement of reduced NO availability in the development of hypertension in hydronephrosis was investigated. Hydronephrosis was induced by ureteral obstruction in young rats. Blood pressure and renal excretion were measured in adulthood, under different sodium conditions, and before and after chronic administration of either N G -nitro-L-arginine methyl ester (L-NAME) or L-arginine. Blood samples for ADMA, SDMA, and L-arginine analysis were taken and the renal tissue was used for histology and determination of NO synthase (NOS) proteins. TGF characteristics were determined by stop-flow pressure technique before and after administration of 7-nitroindazole (7-NI) or L-arginine. Hydronephrotic animals developed salt-sensitive hypertension, which was associated with pressure natriuresis and diuresis. The blood pressure response to L-NAME was attenuated and L-arginine supplementation decreased blood pressure in hydronephrotic animals, but not in the controls. Under control conditions, reactivity and sensitivity of the TGF response were greater in the hydronephrotic group. 7-NI administration increased TGF reactivity and sensitivity in control animals, whereas, in hydronephrotic animals, neuronal NOS (nNOS) inhibition had no effect. L-Arginine attenuated TGF response more in hydronephrotic kidneys than in controls. The hydronephrotic animals displayed various degrees of histopathological changes. ADMA and SDMA levels were higher and the renal expressions of nNOS and endothelial NOS proteins were lower in animals with hydronephrosis. Reduced NO availability in the diseased kidney in hydronephrosis, and subsequent resetting of the TGF mechanism, plays an important role in the development of hypertension.ADMA; tubuloglomerular feedback; L-arginine; L-NAME; telemetry; blood pressure HYPERTENSION IS THE MOST COMMON chronic disorders worldwide and secondary forms of hypertension are found in 5-10% of the hypertensive population, of which most can be linked to renal disease (24). In humans, as well as in experimental models of salt-sensitive hypertension, there is a growing body of evidence pointing at a close relationship between nitric oxide (NO) deficiency and development of hypertension (37).Hydronephrosis due to obstruction at the level of the pelvicureteric junction is a common condition in children, with an incidence in newborns of ϳ1%. The obstruction is mostly partial and congenital of origin. Unilateral hydronephrosis causes salt-sensitive hypertension in both rats (5) and mice (7).The renal function in hydronephrotic animals, measured as renal blood flow and glomerular filtration rate (GFR), is rather...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals

Carlström¹,

Brown²,

Edlund³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…NO production is dependent on the activities of NOS enzymes, whose expression is, in turn, modulated by signaling pathways implicated in inflammation, such as NF-B and MAPKs (9 -11, 13, 14). NO donors protect the kidney in diverse models of renal failure, including ischemic renal failure (15,16), obstructive nephropathy (17), or renal allografts (18). Inhibition of NO synthesis increases susceptibility to kidney ischemia (16,19,20).…”

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confidence: 99%

Inducible Nitric-oxide Synthase Is an Important Contributor to Prolonged Protective Effects of Ischemic Preconditioning in the Mouse Kidney

Park

Byun

Kramers

et al. 2003

Journal of Biological Chemistry

191

165

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Ischemic preconditioning renders the mouse kidney resistant to subsequent ischemia. Understanding the mechanisms responsible for ischemic preconditioning is important for formulating therapeutic strategies aimed at mimicking protective mechanisms. We report that the resistance afforded by 30 min of bilateral kidney ischemia persists for 12 weeks after preconditioning. The protection is reflected by improved postischemic renal function, reduced leukocyte infiltration, reduced postischemic disruption of the actin cytoskeleton, and reduced postischemic expression of kidney injury molecule-1 (Kim-1). The protection is observed in both BALB/c and C57BL/6J strains of mice. Thirty minutes of prior ischemia increases the expression of inducible nitric-oxide synthase (iNOS) and endothelial NOS (eNOS) and the expression of heat shock protein (HSP)-25 and is associated with increased interstitial expression of ␣-smooth muscle actin (␣-SMA), an indication of long term postischemic sequelae. Treatment with N-nitro-L-arginine (L-NNA), an inhibitor of NO synthesis, increases kidney susceptibility to ischemia. Gene deletion of iNOS increases kidney susceptibility to ischemia, whereas gene deletion of eNOS has no effect. Pharmacological inhibition of NOS by L-NNA or L-N6-(1-iminoethyl) lysine (L-NIL, a specific inhibitor of iNOS) mitigates the kidney protection afforded by 30 min of ischemic preconditioning. Fifteen minutes of prior ischemic preconditioning, which does not result in the disruption of the actin cytoskeleton, impairment of renal function, increased interstitial ␣-SMA, or increased iNOS or eNOS expression, but does increase HSP-25 expression, partially protects the kidney from ischemia on day 8 via a mechanism that is not abolished by L-NIL treatment. Thus, iNOS is responsible for a significant component of the long term protection afforded the kidney by ischemic preconditioning, which results in persistent renal interstitial disease, but does not explain the preconditioning seen with shorter periods of ischemia.

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“…Given the multiple functions of arginine 1,2,21 and the fact that a number of therapeutic approaches have been based on alterations in arginine availability, 6,7 it is of importance to investigate the longer-term homeostatic mechanisms elicited in response to a prolonged period of dietary deprivation of arginine and of its major immediate precursors. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…4 An arginine deficiency impairs B cell maturation, 5 and supplementation or restriction of arginine intake have been advocated as therapeutic modalities for different pathophysiologic conditions. 6,7 Despite the functional and physiological significance of arginine, the whole body response and the homeostatic mechanisms elicited during a "long term" dietary restriction of arginine and its immediate metabolic precursors (proline, glutamate and aspartate), have not been previously investigated in healthy adults. Therefore, we have examined whole body, in vivo homeostasis of arginine in healthy adults under conditions of a long term (4 weeks) restriction of dietary arginine and its major precursors (ornithine, proline, glutamate and aspartate).…”

Section: Introductionmentioning

confidence: 99%

Adaptation to a long term (4weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet

Tharakan

Zurakowski

et al. 2008

Clinical Nutrition

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L-Arginine deficiency and supplementation in experimental acute renal failure and in human kidney transplantation

Cited by 78 publications

References 40 publications

Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals

Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals

Inducible Nitric-oxide Synthase Is an Important Contributor to Prolonged Protective Effects of Ischemic Preconditioning in the Mouse Kidney

Adaptation to a long term (4weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet

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