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.

• rosiglitazone
• heat-shock proteins
• deoxycorticosterone acetate-salt
• endothelin-1

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), α-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 α1-subunit, NKCC2, NHE1, and ENaC α-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
• sodium transporters
• aquaporins
• submandibular gland

This study inquired the relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and left ventricular (LV) dysfunction and extracellular water in continuous ambulatory peritoneal dialysis (CAPD) patients. We conducted a cross-sectional study of 30 CAPD patients. Each patient was admitted to the department of internal medicine, Chosun University Hospital between February and October, 2006. Echocardiography was performed using HDI 5000, allowing M-mode, two-dimensional measurement. A multifrequency bioimpedance analyzer was used; extracellular water was calculated as a percentage of total body water and was understood as the index of volume load of CAPD patients. The mean age was 47±12 years. Underlying causes of renal failure were 14 with diabetes mellitus, 7 with hypertension, and 9 with chronic glomerulonephritis. The mean serum NT-proBNP level was 14236.56 (83-35,000) pg/mL. LV mass index and LV ejection fraction were 151.67±42.5 g/m2 and 57.48±12.9%, respectively. The mean extracellular water was 35.97±1.04%. Serum NT-proBNP levels correlated positively with LV mass index (r=0.768, p=0.01) and extracellular water (r=0.866, p=0.01) and negatively with LV ejection fraction (r=-0.808, p=0.01). Serum NT-proBNP levels significantly correlated with LV mass index, LV ejection fraction, and extracellular water. Therefore, serum NT-proBNP levels can be a clinical predictive marker for LV hypertrophy, LV dysfunction, and volume status in CAPD patients.

• continuous ambulatory peritoneal dialysis
• pro-brain natriuretic peptide (1-76)
• extracellular fluid

Injury to the renal microvasculature and inflammatory process may be major factors in the progression of renal disease, therefore, protection of the renal endothelial cell and regulation of inflammatory process may be an important therapeutic target of renal disease. Thus, we evaluated the protective effect of cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) in unilateral ureteral obstruction (UUO)-induced renal fibrosis, cyclosporine A (CsA)-induced renal injury, and the diabetic nephropathy model. In the UUO model, morphologic examination indicated less tubular injury and tubulointerstitial fibrosis in mice that received COMP-Ang1 compared to vehicle-treated mice. Interstitial type I collagen, myofibroblast accumulation, renal surface microvasculature and renal blood flow were higher after treatment with COMP-Ang1 compared to vehicle-treated mice. COMP-Ang1 treatment decreased monocyte/macrophage infiltration, tissue levels of transforming growth factor β1 (TGF-β1), and Smad 2/3 phosphorylation and increased Smad 7 in the obstructed kidney. In CsA-induced renal injury, histologic examination showed significantly decreased CsA-induced tubular damage and tubulointerstitial fibrosis in COMP-Ang1 treated mice. COMP-Ang1 administration also decreased increased macrophage infiltration, adhesion molecule expression, transforming growth factor β1, and Smad 2/3 levels in CsA-treated kidneys, while increasing Smad 7 levels. Laser-Doppler sonographic findings and endothelial factor VIII staining revealed that COMP-Ang1 had a preservative effect on peritubular vasculature. In the diabetic nephropathy model, COMP-Ang1 reduced albuminuria and decreased mesangial expansion, thickening of the glomerular basement membrane and podocyte foot process broadening and effacement. COMP-Ang1 may delay the fibrotic changes in the kidney of diabetic db/db mice through its anti-inflammatory or metabolic effects. In conclusion, COMP-Ang1 may be an endothelium-specific and anti-inflammatory therapeutic modality in fibrotic renal disease.

• angiopoietin-1
• kidney
• endothelial cells

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.

• nitric oxide
• natriuresis
• diuresis
• chronic kidney disease
• acute kidney injury
• hypertension

Prostaglandins (PGs) with best-defined renal functions are PGE2 and prostacyclin (PGI2). These vasodilatory PGs increase renal blood flow and glomerular filtration rate under conditions associated with decreased actual or effective circulating volume, resulting in greater tubular flow and secretion of potassium. Under conditions of decreased renal perfusion, the production of renal PGs serves as an important compensatory mechanism. PGI2 (and possibly PGE2) increases potassium secretion mainly by stimulating secretion of renin and activating the renin-angiotensin system, which leads to increased secretion of aldosterone. In addition, PGE2 is involved in the regulation of sodium and water reabsorption and acts as a counterregulatory factor under conditions of increased sodium reabsorption. PGE2 decreases sodium reabsorption at the thick ascending limb of the loop of Henle probably via inhibition of the Na+-K+-2Cl- cotransporter type 2 (NKCC2). Cyclooxygenase inhibitors may enhance urinary concentrating ability in part through effects to upregulate NKCC2 in the thick ascending limb of Henle`s loop and aquaporin-2 in the collecting duct. Thus, they may be useful to treat Bartter`s syndrome and nephrogenic diabetes insipidus.

• prostaglandins
• kidney
• sodium
• kidney concentrating ability

The kidneys play a fundamental role in the long-term control of arterial pressure by regulating sodium balance and extracellular fluid volume. The renin-angiotensin system (RAS) is at the center of the regulation of hypertension and progressive renal injury. It has gradually become clear that not only systemic RAS, but also intrarenal RAS has specific effects in the pathogenesis and progression of hypertension and renal damage. All of the RAS components are exhibited in the kidney and intrarenal angiotensin II (Ang II) is formed by multiple mechanisms. The demonstration of much enhanced levels of Ang II within specific renal compartments points out selective local regulation of Ang II in the kidney, showing that intrarenal Ang II levels are regulated in a way different from circulating Ang II. The importance of the RAS in involving proper nephrogenesis is also well known, and suppression of the RAS during fetal development may play a key role in mediating the structural and physiological changes observed in models of fetal programming of hypertension.

• kidney
• blood pressure
• renin-angiotensin system
• environment

Vasopressin, a neurohypophyseal peptide hormone, is the endogenous agonist at V1a, V1b, and V2 receptors. The most important physiological function of vasopressin is the maintenance of water homeostasis through interaction with V2 receptors in the kidney. Vasopressin binds to V2 receptor and increases the number of aquaporin-2 at the apical plasma membrane of collecting duct principal cells. That induces high water permeability across the membrane. Several non-peptide vasopressin receptor antagonists have been developed and are being studied primarily for treating conditions characterized by hyponatremia and fluid overload. Further studies are needed to determine how they are best used in these situations.

• vasopressins
• aquaporin 2
• hyponatremia
• vasopressin receptor antagonist

On view of the absent or minimal osmotic diuresis in end stage renal disease, hyperglycemia on maintenance hemolysis as compared to nonketotic hyperosmolar status without underlying advanced renal failure has been noted to show a wide clinical spectrum form severe manifestations by hypertonicity to no clinical manifestations at all. We experienced a 60-year-old man with a known history of type II diabetes mellitus on maintenance hemodialysis for 2 years, who was admitted 4 times within 1 year with hyperglycemia (>500 mg/dL) accompanied by recurrent nausea and vomiting at each admission. However, the calculated effective osmolality (tonicity) in this case ranged only from 286 to 303 mOsm/kg H2O. During the past 6 months following meticulous education for the importance of compliance to medication, especially prokinetics for diabetic gastroparesis, he developed no further episode of hyperglycemia or nausea and vomiting.

• hyperglycemia
• hemodialysis
• hyperosmolality