American journal of physiology. Renal physiology
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Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator of the Rel family. In the renal medulla, TonEBP stimulates genes encoding proteins involved in cellular accumulation of organic osmolytes, the vasopressin-regulated urea transporters (UT-A), and heat shock protein 70. To understand the role of TonEBP in the development of urinary concentrating ability, TonEBP expression during rat kidney development was investigated. ⋯ The adult pattern of TonEBP expression was established at postnatal day 21 coincident with full maturation of the renal medulla. Thus expression of TonEBP in developing kidneys occurred predominantly in the medulla and preceded expression of its target genes, including UT-A. These data suggest that TonEBP contributes to the development of urine-concentrating ability.
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Am. J. Physiol. Renal Physiol. · Nov 2004
Protection of transplant-induced renal ischemia-reperfusion injury with carbon monoxide.
Carbon monoxide (CO), a product of heme metabolism by heme oxygenases, is known to impart protection against oxidative stress. We hypothesized that CO would protect ischemia-reperfusion (I/R) injury of transplanted organs, and the efficacy of CO was studied in the rat kidney transplantation model. A Lewis rat kidney graft, preserved in University of Wisconsin solution at 4 degrees C for 24 h, was orthotopically transplanted into syngeneic rats. ⋯ Further detailed morphological analyses revealed that CO preserved the glomerular vascular architecture and podocyte viability with less apoptosis of tubular epithelial cells and less ED1(+) macrophage infiltration. CO inhalation resulted in improved serum creatinine levels and clearance, and animal survival was significantly improved with CO to 60.5 from 25 days in untreated controls. The study demonstrates that exposure of kidney graft recipients to CO at a low concentration can impart significant protective effects against renal I/R injury and improve function of renal grafts.
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Am. J. Physiol. Renal Physiol. · Nov 2004
Endothelial nitric oxide synthase-deficient mice exhibit increased susceptibility to endotoxin-induced acute renal failure.
Acute renal failure (ARF) in septic patients drastically increases the mortality to 50-80%. Nitric oxide (NO) has been shown to be increased in sepsis. Endothelial nitric oxide synthase (eNOS) is one of the major regulators of arterial blood pressure and regional blood flow; however, its in vivo role in septic ARF is still unclear. ⋯ Although GFR (154 +/- 22 microl/min, n = 8) and RBF (1.19 +/- 0.05 ml/min, n = 9) remained unchanged with the 1.0-mg/kg dose of LPS in the wild-type mice, GFR (83 +/- 18 vs. 140 +/- 10 microl/min, n = 6, P < 0.01) and RBF (0.36 +/- 0.04 vs. 0.62 +/- 0.05 ml/min, n = 6, P < 0.01) decreased significantly in the eNOS knockout mice. Fractional excretion of sodium increased significantly in eNOS knockout mice during endotoxemia (3.61 +/- 0.78, n = 7 vs. 0.95 +/- 0.14, n = 6, P < 0.01), whereas it remained unchanged in the wild-type mice (0.59 +/- 0.16, n = 9 vs. 0.42 +/- 0.05, n = 6, P = not significant). In summary, eNOS knockout mice have increased RVR and are more susceptible to endotoxemic ARF than wild-type mice despite higher MAP.