American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Nov 2008
ReviewRole of three-dimensional architecture in the urine concentrating mechanism of the rat renal inner medulla.
Recent studies of three-dimensional architecture of rat renal inner medulla (IM) and expression of membrane proteins associated with fluid and solute transport in nephrons and vasculature have revealed structural and transport properties that likely impact the IM urine concentrating mechanism. These studies have shown that 1) IM descending thin limbs (DTLs) have at least two or three functionally distinct subsegments; 2) most ascending thin limbs (ATLs) and about half the ascending vasa recta (AVR) are arranged among clusters of collecting ducts (CDs), which form the organizing motif through the first 3-3.5 mm of the IM, whereas other ATLs and AVR, along with aquaporin-1-positive DTLs and urea transporter B-positive descending vasa recta (DVR), are external to the CD clusters; 3) ATLs, AVR, CDs, and interstitial cells delimit interstitial microdomains within the CD clusters; and 4) many of the longest loops of Henle form bends that include subsegments that run transversely along CDs that lie in the terminal 500 microm of the papilla tip. Based on a more comprehensive understanding of three-dimensional IM architecture, we distinguish two distinct countercurrent systems in the first 3-3.5 mm of the IM (an intra-CD cluster system and an inter-CD cluster system) and a third countercurrent system in the final 1.5-2 mm. Spatial arrangements of loop of Henle subsegments and multiple countercurrent systems throughout four distinct axial IM zones, as well as our initial mathematical model, are consistent with a solute-separation, solute-mixing mechanism for concentrating urine in the IM.
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Am. J. Physiol. Renal Physiol. · Nov 2008
Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury.
IL-18 function is neutralized in IL-18 binding protein transgenic (IL-18BP Tg) mice. First, we determined whether IL-18BP Tg mice are protected against ischemic acute kidney injury (AKI). Ischemic AKI was induced by bilateral renal pedicle clamping. ⋯ CXCL1 was significantly decreased in macrophage-depleted vs. control AKI mice. In summary, in ischemic AKI in mice, 1) IL-18BP Tg mice are functionally and histologically protected, 2) macrophage infiltration in the kidney and CXCL1 are significantly reduced in IL-18BP Tg mice, and 3) macrophage depletion significantly reduces CXCL1 in the kidney. In conclusion, protection against ischemic AKI in IL-18BP Tg mice is associated with less macrophage infiltration and less production of CXCL1 in the kidney.
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Am. J. Physiol. Renal Physiol. · Nov 2008
TRPV1 mediates the uterine capsaicin-induced NMDA NR2B-dependent cross-organ reflex sensitization in anesthetized rats.
Spinal cord-mediated cross-organ sensitization between the uterus and the lower urinary tract may underlie the high concurrence of obstetrical/gynecological inflammation and chronic pelvic pain syndrome characterized by urogenital pain. However, the neural pathway and the neurotransmitters involved are still unknown. We tested the hypothesis that the excitation of capsaicin-sensitive primary afferent fibers arising from the uterus through the stimulation of transient receptor potential vanilloid 1 (TRPV1) induces cross-organ sensitization on the pelvic-urethra reflex activity. ⋯ Activation of capsaicin-sensitive primary afferent fibers by capsaicin instillation into the uterine horn sensitized the pelvic-urethra reflex activity that was reversed by an intrauterine pretreatment with capsaizepine, a TRPV1-selective antagonist. Intrathecal injection of AP5, a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, and Co-101244, an NMDA NR2B-selective antagonist, both abolished the cross-organ reflex sensitization caused by capsaicin instillation. These results demonstrated that TRPV1 plays a crucial role in contributing to the capsaicin-sensitive primary afferent fibers mediating the glutamatergic NMDA-dependent cross-organ sensitization between the uterus and the lower urinary tract when there is a tissue injury.
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Am. J. Physiol. Renal Physiol. · Oct 2008
Role of NF-kappaB and PI 3-kinase/Akt in TNF-alpha-induced cytotoxicity in microvascular endothelial cells.
The interaction of tumor necrosis factor (TNF)-alpha with the endothelium is a pivotal factor during endotoxemia. Inflammatory conditions are characterized by the activation of the transcription factor NF-kappaB and the expression of inflammatory mediators. Previous reports indicate that inhibition of NF-kappaB activation during sepsis may be beneficial to the microvasculature. ⋯ The present results therefore demonstrate a cytotoxic effect of TNF-alpha in microvascular endothelial cells which can be attenuated by NF-kappaB inhibition. In addition, PI3-kinase/Akt activation during TNF-alpha exposure may represent a compensatory anti-necrotic and anti-apoptotic pathway. The cytoprotective effects of NF-kappaB inhibition and PI3-kinase/Akt activation may have potential implications in the treatment of endotoxemia and septic shock.
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Am. J. Physiol. Renal Physiol. · Sep 2008
alpha2-Adrenergic agonists protect against radiocontrast-induced nephropathy in mice.
Radiocontrast nephropathy (RCN) is a common clinical problem for which there is no effective therapy. Utilizing a murine model, we tested the hypothesis that alpha(2)-adrenergic receptor agonists (clonidine and dexmedetomidine) protect against RCN induced with iohexol (a nonionic low-osmolar radiocontrast). C57BL/6 mice were pretreated with saline, clonidine, or dexmedetomidine before induction of RCN. ⋯ Iohexol caused a direct dose-dependent reduction of HK-2 and rat pulmonary microvascular endothelial cell viability, but alpha(2)-agonists failed to preserve the viability of both cell types. We conclude that alpha(2)-adrenergic receptor agonists protect mice against RCN by preserving outer medullary renal blood flow. As alpha(2)-agonists are widely utilized during the perioperative period, our findings may have significant clinical relevance to improving outcomes following radiocontrast exposure.