What Is the Ideal Entry Point for Transforaminal Endoscopic Lumbar Discectomy?

Objective@#: The method of approach during transforaminal endoscopic lumbar discectomy (TELD) has been the subject of repeated study. However, the ideal entry point during TELD has not been studied in detail. Therefore, this study investigated the ideal entry point for avoiding complications using computed tomography (CT) scans obtained from patients in the prone position. @*Methods@#: Using CT scans obtained from patients in the prone position, we checked for retroperitoneal or visceral violations and measured the angles of approach with five conventional approach lines drawn on axial CT scans at each disc space level (L2–3, L3–4, and L4–5). We also determined the ideal entry point distance and approach angles for avoiding retroperitoneal or visceral violations.Correlation analysis was performed to identify the patient characteristics related to the ideal entry point properties. @*Results@#: We found that the far lateral approach at the L2–3 level resulted in high rates of visceral violation. However, rates of visceral violation at the L3–4 and L4–5 levels were remarkably low or absent. The ideal angles of approach decreased moving caudally along the spine, and the ideal entry point distances increased moving caudally along the spine. Weight, body mass index (BMI), and the depth of the posterior vertebral line from the skin were positively associated with the distance of the ideal entry point from the midline. @*Conclusion@#: We reviewed the risk of the extreme lateral approach by analyzing rates of retroperitoneal and visceral violations during well-known methods of approach. We suggested an ideal entry point at each level of the lumbar spine and found a positive correlation between the distance of the entry point to the midline and patient characteristics such as BMI, weight, and the depth of the posterior vertebral line from the skin.

Effects of Tamoxifen in Deoxycorticosterone Acetate-salt Hypertensive Nephropahty

BACKGROUND: The present study was designed to evaluate the possible renoprotective effects of tamoxifen in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats and its role in inflammation and fibrosis in the kidney. METHODS: Male Sprague-Dawley rats, weighing 180 to 200 g, were used. All rats underwent unilateral nephrectomy. One week later, one group of rats (n = 8) was implanted with DOCA strips (200 mg/kg) and another group of rats (n = 8) was implanted with DOCA strips with co-treated with tamoxifen (10 mg/kg) through gavage feeding. Rats that did not implanted DOCA strips served as controls (n = 6). Two weeks later, the systolic blood pressure (SBP) was measured by tail-cuff method. The protein expression of transforming growth factor-beta (TGF-beta), Smad, alpha-smooth muscle actin (alpha-SMA), E-cadherin, ED-1, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) was determined in the kidney by immunoblotting. The mRNA expression of tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1) was determined by real-time polymerase chain reaction. RESULTS: In DSH rats, SBP was increased, which was not affected by tamoxifen treatment. Serum creatinine level was comparable in DSH rats compared with controls, which was not affected by tamoxifen treatment. In DSH rats, the protein expression of TGF-beta, Smad 2/3, Smad 4, alpha-SMA, ED-1, COX-2, iNOS was increased compared with controls, and these changes were attenuated by tamoxifen treatment except that of TGF-beta. The mRNA expression of TNF-alpha, MCP-1, and VCAM-1 was increased, and expression of MCP-1 and VCAM-1 was counteracted by tamoxifen treatment. CONCLUSIONS: Tamoxifen is effective in preventing the progression of nephropathy in DSH rats, the mechanism of which is associated with anti-inflammation and anti-fibrotic effects.

Antiapoptotic Effect of Paricalcitol in Gentamicin-induced Kidney Injury

While the anti-apoptotic effect of paricalcitol has been demonstrated in various animal models, it is not yet clear whether paricalcitol attenuates the apoptosis in gentamicin (GM)-induced kidney injury. We investigated the effect of paricalcitol on apoptotic pathways in rat kidneys damaged by GM. Rats were randomly divided into three groups: 1) Control group (n=8), where only vehicle was delivered, 2) GM group (n=10), where rats were treated with GM (150 mg/kg/day) for 7 days, 3) PARI group (n=10), where rats were co-treated with paricalcitol (0.2 microg/kg/day) and GM for 7 days. Paricalcitol attenuated renal dysfunction by GM administration in biochemical profiles. In terminal deoxynucleotidyl transferase dUTP nick end labeling staining, increased apoptosis was observed in GM group, which was reversed by paricalcitol co-treatment. Immunoblotting using protein samples from rat cortex/outer stripe of outer medulla showed increased Bax/Bcl-2 ratio and cleaved form of caspase-3 in GM group, both of which were reversed by paricalcitol. The phosphorylated Jun-N-terminal kinase (JNK) expression was increase in GM, which was counteracted by paricalcitol. The protein expression of p-Akt and nitro-tyrosine was also enhanced in GM-treated rats compared with control rats, which was reversed by paricalcitol co-treatment. Paricalcitol protects GM-induced renal injury by antiapoptotic mechanisms, including inhibition of intrinsic apoptosis pathway and JNK.

Altered Regulation of Endothelin, Atrial Natriuretic Peptide, and Nitric Oxide Systems in Angiotensin II-induced Hypertension

BACKGROUND: The present study aimed to determine the changes of endothelin (ET), nitric oxide, and atrial natriuretic peptide (ANP) systems in the kidney and aorta in angiotensin (Ang) II-induced hypertension. METHODS: Male Sprague-Dawley rats were used. Ang II (100 ng.min-1.kg-1) was infused through entire time course. Fourteen days after beginning the regimen, aorta and kidney were taken. The protein expression of nitroc oxide synthase (NOS) was determined by semiquantitative immunoblotting. The mRNA expression of components of ET, NOS, ANP system was determined by real-time polymerase chain reaction. RESULTS: Hypertension was developed in the experimental group. mRNA expression of ET-1 in the aorta and kidney was increased. The protein expression of endothelial NOS (eNOS) was decreased in the aorta, while that of inducible NOS and neuronal NOS remained unaltered. mRNA expression of ANP, natriuretic peptide type (NPR)-A, and NPR-C was not changed in the aorta. CONCLUSIONS: Based on these results, it seems that in Ang II-induced hypertensive rats, increased expression of ET-1 in the aorta and kidney, and decreased eNOS expression in the aorta contribute to the pathogenesis of hypertension.

Activation of the Renal PI3K/Akt/mTOR Signaling Pathway in a DOCA-Salt Model of Hypertension / 전남의대학술지

The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-beta1, and alpha-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.

Altered Regulation of Renal Acid Base Transporters in Response to Ammonium Chloride Loading in Rats

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of NH4Cl for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), Na-K+ ATPase, H(+)-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, H(+)-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, H(+)-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, H(+)-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.

Activation of the Renal PI3K/Akt/mTOR Signaling Pathway in a DOCA-Salt Model of Hypertension / 전남의대학술지

The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-beta1, and alpha-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.

Altered Regulation of Renal Nitric Oxide and Atrial Natriuretic Peptide Systems in Lipopolysaccharide-induced Kidney Injury

Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 mg.kg-1) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immunoblotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.

Decreased expression of Na,K-ATPase in the kidneys of rats with two-kidney, one-clip hypertension / 대한내과학회지

BACKGROUND/AIMS: This study investigated the role of Na,K-ATPase, the local renin-angiotensin-aldosterone system (RAAS), and atrial natriuretic peptide (ANP) system in the pathogenesis of renal tubular dysfunction and hypertension in rats with two-kidney, one-clip (2K1C) hypertension. METHODS: Adult male Sprague-Dawley rats were made 2K1C hypertensive for 4 weeks. The renal expression of Na,K-ATPase was determined by immunoblotting. The mRNA expression of renin, angiotensin-converting enzyme (ACE), aldosterone synthase (CYP11B2), mineralocorticoid receptor (MR), and the ANP system were determined in the kidney using real-time polymerase chain reaction. RESULTS: The blood pressure was increased in the 2K1C rats, compared with controls. The plasma renin activity and serum aldosterone concentrations were increased, as were the urine output and fractional excretion of sodium. The expression of Na,K-ATPase protein was decreased in the clipped kidney, as compared with the control kidney, while it remained unchanged in the contralateral kidney. The mRNA expression of renin, ACE1, CYP11B2, and MR was increased in the clipped kidney, but unchanged in the non-clipped kidney. The mRNA expression of ACE2 did not differ between the groups. The expression of ANP mRNA was increased in both clipped and non-clipped kidneys, as compared with control kidneys. CONCLUSIONS: The enhanced activity of the local RAAS may result in to ischemic tubular injury and the development of hypertension in 2K1C rats. The downregulation of Na,K-ATPase associated with tubular injury in the clipped kidney may account for the impaired tubular sodium reabsorption in 2K1C hypertension.

Pathophysiological Implications of Sodium Transporters and Water Channels in the Kidney / 대한신장학회지

Renal sodium and water reabsorption occurs through epithelial sodium transporters and aquaporin (AQP) water channels in various segments of tubules. We have demonstrated altered regulation of these transporters and channels in various pathophysiological conditions. In nephrotic syndrome and liver cirrhosis, expression of epithelial sodium channels (ENaC) was increased in the late distal convoluted tubule, connecting tubule, and collecting duct. In spontaneously hypertensive rats, the expression of Na,K-ATPase as well as that of ENaC was increased. In contrast, AQP1-3 and sodium transporters was decreased in the kidney from deoxycorticosterone acetate-salt hypertension. In two-kidney, one clip hypertension, the expression of Na,K-ATPase, NHE3, NKCC2 and ENaC subunits was decreased in the clipped kidney while remained unchanged in the contralateral kidney. We have also shown an increased activity of renal atrial natriuretic peptide system in postobstructive natriuresis/ diuresis. In acute kidney injury (cisplatin-, gentamicin- and ischemia/reperfusion-induced), the expression of Na,K-ATPase, NHE3, NKCC2 and AQP1-3 was decreased. The altered regulation of sodium transporters and AQP may be causally related with various kidney diseases and hypertension.

Pathophysiological Implications of Sodium Transporters and Water Channels in the Kidney / 대한신장학회지

Renal sodium and water reabsorption occurs through epithelial sodium transporters and aquaporin (AQP) water channels in various segments of tubules. We have demonstrated altered regulation of these transporters and channels in various pathophysiological conditions. In nephrotic syndrome and liver cirrhosis, expression of epithelial sodium channels (ENaC) was increased in the late distal convoluted tubule, connecting tubule, and collecting duct. In spontaneously hypertensive rats, the expression of Na,K-ATPase as well as that of ENaC was increased. In contrast, AQP1-3 and sodium transporters was decreased in the kidney from deoxycorticosterone acetate-salt hypertension. In two-kidney, one clip hypertension, the expression of Na,K-ATPase, NHE3, NKCC2 and ENaC subunits was decreased in the clipped kidney while remained unchanged in the contralateral kidney. We have also shown an increased activity of renal atrial natriuretic peptide system in postobstructive natriuresis/ diuresis. In acute kidney injury (cisplatin-, gentamicin- and ischemia/reperfusion-induced), the expression of Na,K-ATPase, NHE3, NKCC2 and AQP1-3 was decreased. The altered regulation of sodium transporters and AQP may be causally related with various kidney diseases and hypertension.

Changes of Atrial Natriuretic Peptide System in Rats with Puromycin Aminonucleoside-Induced Nephrotic Syndrome

Sodium retention is a hallmark of nephrotic syndrome. We investigated whether sodium retention is associated with changes of natriuretic peptide system at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndrome. At day 7 after PAN (puromycin aminonucleoside) injection, the urinary excretion of sodium was decreased, along with the development of ascites and positive sodium balance. The plasma and urinary ANP (atrial natriuretic peptide) immunoreactivities were increased. ANP mRNA expression was increased in the heart and kidney, whereas that of NPR (natriuretic peptide receptor)-A and NPR-C mRNA was decreased in the kidney. The expression of NEP was decreased in the kidney. At day 14, urinary excretion of sodium did not differ from the control. The plasma ANP level and heart ANP mRNA expression returned to their control values. The expression of ANP mRNA in the kidney was increased in association with increased urinary ANP immunoreactivities. The expression of NPR-A in the kidney became normal, whereas that of NPR-C kept decreased. The expression of NEP (neutral endopeptidase) remained decreased. These findings suggest that the increased renal ANP synthesis in association with decreased metabolism via NEP and NPR-C may play a compensatory role against the development of sodium retention in nephrotic syndrome. The decreased of NPR-A expression in the kidney may contribute to the ANP resistance at day 7. The subsequent recovery of NPR-A expression may play a role in promoting sodium excretion in later stage (at day 14).

Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na+/K+-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT.

Effects of Rosiglitazone on Heat Shock Protein and the Endothelin System in Deoxycorticosterone Acetate-Salt Hypertensive Rats

The deoxycorticosterone acetate (DOCA)-salt rat is known as a model of volume dependent hypertension and characterized by increased cardiac endothelin-1 (ET-1) content. Recently, it has been reported that rosiglitazone (RGT), a peroxisome proliferator-activated subtype gamma receptor agonist, shows blood pressure lowering effect. We investigated whether DOCA-salt hypertension is associated with altered expression of heat shock proteins (HSP) and ET-1 in the heart, aorta, and kidney, and whether RGT changes HSP expression and ET-1 in association with its blood pressure lowering effect. Two weeks after the silastic DOCA (200 mg/kg) strips implantation, DOCA-salt rats were randomly divided to receive control diet with or without RGT (10 mg/kg/day) for another 2 weeks. The mRNA expression of ET-1 was determined by real time polymerase chain reaction. The expression of HSP was determined by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was markedly increased, while creatinine clearance decreased. RGT treatment attenuated high blood pressure and decreased creatinine clearance in DOCA-salt rats. The mRNA expression of ET-1 was increased in DOCA-salt rats compared to controls, which was counteracted by RGT treatment. The protein expression of HSP70, HSP32, and HSP25 was increased in the kidney and heart in DOCA-salt rats, which was attenuated by RGT treatment in the kidney, but not in the heart. In conclusion, increased expression of ET-1 may play a role in the pathogenesis of hypertension in DOCA-salt rats, which was counteracted by the treatment of RGT. Up-regulation of HSP70, HSP32, and HSP25 in the kidney and heart may play a role in organ protection against a variety of stresses.

Altered Expression of Sodium Transporters and Water Channels in the Submandibular Gland of Rats Treated with Nitric Oxide Synthesis Inhibitors

A role of nitric oxide (NO) in the regulation of sodium transporters and water channels in the salivary gland was investigated. Male Sprague-Dawley rats were treated with NG-nitro-L-arginine methyl ester (L- NAME, 100 mg/L drinking water) for 1 week. The control group was supplied with normal tap water. The expression of Na+,K+-ATPase, type 2 Na+/K+/2Cl- cotransporter (NKCC2), type 1 Na+/H+ exchanger (NHE1), alpha-subunit of epithelial sodium transporter (ENaC), and aquaporin-5 (AQP5) and aquaporin-1 (AQP1) proteins were determined in the submandibular gland by Western blot analysis. Following the treatment with L-NAME, the expression of Na+,K+-ATPase alpha1-subunit, NKCC2, NHE1, and ENaC alpha- subunit increased significantly. On the contrary, the expression of AQP5 was significantly decreased, while that of AQP1 was not significantly altered. These findings indicate that the sodium transporters and water channels may be under a tonic regulatory influence of NO in the salivary gland.

Nitric Oxide in the Kidney: Its Physiological Role and Pathophysiological Implications

Nitric oxide has been implicated in many physiologic processes that influence both acute and long-term control of kidney function. Its net effect in the kidney is to promote natriuresis and diuresis, contributing to adaptation to variations of dietary salt intake and maintenance of normal blood pressure. A pretreatment with nitric oxide donors or L-arginine may prevent the ischemic acute renal injury. In chronic kidney diseases, the systolic blood pressure is correlated with the plasma level of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. A reduced production and biological action of nitric oxide is associated with an elevation of arterial pressure, and conversely, an exaggerated activity may represent a compensatory mechanism to mitigate the hypertension.

Altered Regulation of Water Channels and Sodium Transporters in Fasting-induced Polyuria in Rat Kidney / 대한신장학회잡지

PURPOSE: Starvation causes impairment in the urinary concentration ability. However, the molecular basis for the impaired urinary concentration and polyuria remains undefined. We examined the effects of food deprivation on the water handling by the kidney and it's regulatory mechanism. METHODS: Sprague-Dawley rats were used. They were placed in metabolic cages and deprived of food but had free access to water for 24 hours. Control rats had free access to both water and food. Protein expression of aquaporin-2 (AQP2) and Na+-K+-2Cl- cotransporter (NKCC2) was determined in the kidney by Western blot analysis. Protein expression of type VI adenylyl cyclase and prostaglandin E2 synthase (PGES) was determined. Urinary PGE2 excretion was also determined by radioimmunoassay. RESULTS: Food deprivation (FD) resulted in impaired urinary concentration associated with decreased tubular water reabsorption and increased urine output. The expression of AQP2 proteins was significantly decreased in the inner stripe of the outer medulla (ISOM). The expression of NKCC2 was not affected in ISOM. The adenylyl cyclase VI expression was increased in ISOM in FD rats. The protein expression of PGES was decreased in the cortex/OSOM and ISOM. The 24 hr urinary excretion of PGE2 was significantly decreased in FD rats compared with controls. CONCLUSION: These findings indicate that FD-induced urinary concentration defect may related to a reduced abundance of AQP2 in the kidney. It is also suggested that the primary impairment in the pathway to the activation of AQP2 in food deprivation is independent of vasopressin/cAMP or prostaglandin activity.

Effects of Antioxidant Drugs in Rats with Acute Renal Injury

Acute renal failure is mainly caused by ischemia/reperfusion (I/R) injury or nephrotoxic drugs, in which reactive oxygen species (ROS) may play an important role. Therefore, antioxidants are expected to decrease the vulnerability of renal injury associated with oxidative challenges. alpha-Lipoic acid (alpha-LA), potent antioxidant, could act as ROS scavengers, iron chelators and enzyme modulators. In rats with acute renal injury, dysregulation of aquaporin (AQP) water channels and sodium transporters has been noted. I/R injury or cisplatin induced marked down-regulation of AQP1, AQP2 and AQP3 water channels, and type-3 Na-H exchanger, Na,K-ATPase, and Na-K-2Cl cotransporters, in association with impairment of urinary concentration and tubular sodium reabsorption. Treatment with alpha-LA prevented the dysregulation of AQP channels and sodium transporters, along with improved urinary concentrating capability and renal sodium reabsorption.

Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney / 대한신장학회지

PURPOSE: An altered activity of vasoactive hormones as well as aldosterone synthase (CYP11B2) in the kidney may involve the pathogenesis of gentamicin-induced nephropathy. The present study was designed to investigate whether there are changes of local renin-angiotensin-aldosterone system (RAAS) and endothelin (ET) in the kidney of gentamicin-induced nephropathy in rats. METHODS: Male Sprague-Dawley rats (180-200 g) were intramuscularly injected with gentamicin (100 mg/kg per day) for 5 days. Vehicle was given for the control rats. The mRNA expression of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET system and transforming grow factor-beta1 (TGF-beta1) was determined in the kidney by real-time polymerase chain reaction. The protein expression of TGF-beta in the kidney was determined by immunoblotting and immunohistochemistry. RESULTS: Following the gentamicin treatment, a renal failure was noted as evidenced by increased serum concentrations of creatinine along with a decrease of its clearance. TGF-beta1 expression was significantly increased in the kidney in gentamicin treated rats compared with that in controls. The abundance of ET-1 mRNA was significantly increased. The endothelin type A receptor expression was decreased while endothelin type B receptor was not changed. The expression of angiotensin converting enzyme 1 (ACE1) and ACE2 was decreased, whereas renin expression was not changed. The CYP11B2 expression was significantly increased in gentamicin treated rats, while mineralocorticoid receptor expression was not changed. CONCLUSION: The expression of ET-1 and CYP11B2 was up-regulated which may play a role in the pathogenesis of gentamicin-induced nephropathy.

Altered Regulation of type 3 Na+/H+ exchanger, type 1 Na+/HCO3- cotransporter, and Na+,K+-ATPase in the Kidney of Rats with Experimental Rhabdomyolysis

Metabolic acidosis was shown to correlate with deterioration of renal function in patients with rhabdomyolysis. The present study was aimed to investigate whether the changes of type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), and Na+,K+-ATPase alpha1 subunit may play a role in the pathogenesis of metabolic acidosis in glycerol-induced experimental rhabdomyolysis. Male Sprague-Dawley rats were deprived of fluid intake for 24 hours, and then were injected with 50% glycerol in normal saline (10 mL/kg, intramuscularly). At 24 hours after the glycerol injection, rats were sacrificed by decapitation. Control rats were injected with normal saline. The protein expression of NHE3, NBC1 and Na+,K+-ATPase alpha1 subunit was determined in the cortex of the kidney by immunoblotting and immunohistochemistry. Following the treatment of glycerol, creatinine clearance was significantly decreased, and high anion gap metabolic acidosis developed. In the experimental group, the expression of Na+,K+-ATPase alpha1 subunit was significantly decreased in the cortex of the kidney. On the contrary, the expression of NHE3 and NBC1 was significantly increased. Immunohistochemical analyses confirmed the immunoblotting data. In conclusion, the coordinate up-regulation of NHE3 and NBC1 may play an adaptive role against the metabolic acidosis in glycerol-induced rhabdomyolysis.