L-Arginine counteracts nitric oxide deficiency and improves the recovery phase of ischemic acute renal failure in rats

Schneider, Reinhard; Raff, Ulrike; Vornberger, Nicole; Schmidt, Monika; Freund, R.; Reber, Mark; Schramm, Lothar; Gambaryan, Stepan; Wanner, Christoph; Schmidt, Harald; Galle, Jan

doi:10.1046/j.1523-1755.2003.00063.x

Cited by 84 publications

(88 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Experiments were performed as published recently (24,27), where I/R injury was induced by bilateral clamping of renal arteries for 45 min. Female Sprague-Dawley rats (200 to 250 g body wt) were obtained from Charles River (Kissleg, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Inulin and PAH clearances were determined as described recently (27). Thereafter, net secretion of PAH (PNS) was calculated as described below.…”

Section: Measurement Of Clearances and Pah Net Secretionmentioning

confidence: 99%

“…Thus we hypothesized that the impairment of organic anion extraction mentioned above may be due to a decreased expression of OAT1 or OAT3. We investigated this in a well-established rat model of ischemic acute renal failure (iARF) (24,27). In fact, the determination of inulin clearance, PAH clearance, and net secretion of PAH and the amount of mRNA and protein of OAT1 and OAT3 indicate that expression of both OAT1 and OAT3 is transiently downregulated after ischemia-reperfusion (I/R) injury.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion ofpara-aminohippurate after ischemic acute renal failure in rats

Schneider

Sauvant²,

Betz³

et al. 2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

M. Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion of para-aminohippurate after ischemic acute renal failure in rats. Am J Physiol Renal Physiol 292: F1599 -F1605, 2007. First published January 23, 2007; doi:10.1152/ajprenal.00473.2006.-Ischemic acute renal failure (iARF) was described to reduce renal extraction of the organic anion para-aminohippurate (PAH) in humans. The rate-limiting step of renal organic anion secretion is its basolateral uptake into proximal tubular cells. This process is mediated by the organic anion transporters OAT1 and OAT3, which both have a broad spectrum of substrates including a variety of pharmaceutics and toxins. Using a rat model of iARF, we investigated whether impairing the secretion of the organic anion PAH might be associated with downregulation of OAT1 or OAT3. Inulin and PAH clearance was determined starting from 6 up to 336 h after ischemiareperfusion (I/R) injury. Net secretion of PAH was calculated and OAT1 as well as OAT3 expression was analyzed by RT-PCR and Western blotting. Inulin and PAH clearance along with PAH net secretion were initially diminished after I/R injury with a gradual recovery during follow-up. This initial impairment after iARF was accompanied by decreased mRNA and protein levels of OAT1 and OAT3 in clamped animals compared with sham-operated controls. In correlation to the improvement of kidney function, both mRNA and protein levels of OAT1 and OAT3 were upregulated during the follow-up. Thus decreased expression of OAT1 and OAT3 is sufficient to explain the decline of PAH secretion after iARF. As a result, this may have substantial impact on excretion kinetics and half-life of organic anions. As a consequence, the biological effects of a variety of organic anions may be affected after iARF. organic anion transporter 1; organic anion transporter 3; proximal tubule; basolateral uptake; renal plasma flow; glomerular filtration; inulin; clearance; PAH net secretion THE ORGANIC ANION TRANSPORT system of the renal proximal tubule plays a crucial role in the excretion of a variety of potentially toxic compounds (22,35). This system consists of organic anion exchangers located at the basolateral membrane and a less well-characterized transport step at the apical membrane (8). The classical basolateral organic anion exchanger is the terminal step in a tertiary active transport system, dependent on an inward-directed Na ϩ gradient to drive the uptake of ␣-ketoglutarate (␣KG), which is then exchanged for organic anions (7,11,23). It has been shown that OAT1 represents characteristics of the basolateral, polyspecific transporter for organic anions (30), which had been functionally described since substantial time (23). Recently, new evidence has indicated that OAT3 (16), which is also located in the basolateral renal proximal tubular membrane, works as an exchanger for organic anions and dicarboxylates, too (32). Moreover, additional homologs have been cloned and were called OAT2 (28), OAT4 (4), OAT5 (40), and OAT6...

show abstract

Section: Methodsmentioning

confidence: 99%

“…Inulin and PAH clearances were determined as described recently (27). Thereafter, net secretion of PAH (PNS) was calculated as described below.…”

Section: Measurement Of Clearances and Pah Net Secretionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion ofpara-aminohippurate after ischemic acute renal failure in rats

Schneider

Sauvant²,

Betz³

et al. 2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…The role of nitric oxide (NO) in renal IR injury has been extensively investigated (8,26,28,34,41,46,50). However, the involvement of the NO downstream signaling pathway, cGMP and cGMP-dependent protein kinase (PKG), in renal IR injury has not been investigated.…”

mentioning

confidence: 99%

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

Tong

Maimaitiyiming

et al. 2012

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury. Am J Physiol Renal Physiol 302: F561-F570, 2012. First published December 7, 2011 doi:10.1152/ajprenal.00355.2011.-cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/ activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG

show abstract

“…In another study, Weight et al (16) emphasized that L-NAME causes no significant alteration in the histology in rats that underwent renal I/R. Schneider et al (17) suggested that in vivo acute L-arginine administration has Table 1. Statistically data with matched normal dissociation favorable effects on renal ischemia.…”

Section: Lahera Et Al (4) Performed Hemodynamic Examinations To Keepmentioning

confidence: 99%

Effect of L-arginine on Hemodynamic, Biochemical, and Histopathological Outcomes in a New Zealand Rabbit Model of Renal Ischemia–Reperfusion Injury

Özülkü¹,

Aygün²

2016

JAREM

View full text Add to dashboard Cite

Thirty-minute suprarenal occlusion was performed in all animals. The rabbits in both groups received an isotonic fluid (Mediflex® 0.9% NaCl, Eczacıbaşı-Baxter, İstanbul, Turkey) infusion at a dosage of 4 milliliters (mL)/kilograms (kg)/hours (h) over the course Methods: Forty white New Zealand rabbits were used. The rabbits were divided into two groups as the control group (n=20) and L-arginine group (n=20). They were monitored by cannulating the auricular and femoral arteries. An aortic occlusion catheter was inserted through the contralateral femoral artery and was extended to the distal aspect of the left subclavian artery; it was then inflated, and occlusion was performed for 30 min. All rabbits received 4 mL/kg/h of NaCl infusion during the course of occlusion and within the first 60 min of reperfusion. In the L-arginine group, L-arginine was infused at a dosage of 3 mg/kg/h through the auricular vein during the first 60 min of occlusion and perfusion. Blood samples for biochemical parameters [glucose, lactate, hematocrit, blood urea nitrogen (BUN), and serum creatinine] were obtained in the peri-ischemic period, in the 20 th minute of reperfusion, and just before sacrificing (48 th hour). A histopathological examination was performed in both renal tissues. Histopathological scoring was performed by taking tubular epithelial cell flattening, brush border loss, cytoplasmic vacuolization, cell necrosis, and tubular lumen obstruction into consideration. All animals were sacrificed 48 h after the procedure.Results: A significant difference was found between the L-arginine and control groups in terms of the hemodynamic outcomes and 48 th hour BUN and serum creatinine levels (p<0.05). The histopathological examination revealed a mean score of 3.2±0.89 in the control group and 2.60±0.68 in the L-arginine group (p<0.05) (p=0.022). Conclusion:It can be suggested that L-arginine reduces renal ischemia-reperfusion injury and in particular, the histopathological effects. (JAREM 2016; 6: 24-30)

show abstract

L-Arginine counteracts nitric oxide deficiency and improves the recovery phase of ischemic acute renal failure in rats

Cited by 84 publications

References 45 publications

Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion ofpara-aminohippurate after ischemic acute renal failure in rats

Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion ofpara-aminohippurate after ischemic acute renal failure in rats

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

Effect of L-arginine on Hemodynamic, Biochemical, and Histopathological Outcomes in a New Zealand Rabbit Model of Renal Ischemia–Reperfusion Injury

Contact Info

Product

Resources

About