American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Nov 2012
Renal cortical hemopexin accumulation in response to acute kidney injury.
Hemopexin (Hpx) is a liver-generated acute phase reactant that binds and neutralizes prooxidant free heme. This study tested whether acute kidney injury (AKI) triggers renal Hpx accumulation, potentially impacting heme Fe-mediated tubular injury. Mice were subjected to glycerol, cisplatin, ischemia-reperfusion (I/R), or endotoxemic [lipopolysaccharide (LPS)] AKI. ⋯ In addition, purified Hpx blunted free Fe-mediated HK-2 cell death. In sum, these data indicated that AKI-associated hepatic stress generates Hpx, which gains renal tubule access. Given its ability to bind free heme and mitigate free Fe toxicity, Hpx loading can potentially confer cytoprotective effects.
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Am. J. Physiol. Renal Physiol. · Nov 2012
ReviewTarget organ cross talk in cardiorenal syndrome: animal models.
The combination of chronic kidney disease (CKD) and heart failure (HF) is associated with an adverse prognosis. Although clinical studies hint at a specific bidirectional interaction between HF and CKD, insight into the pathogenesis of cardiorenal syndrome (CRS) remains limited. We review available evidence on cardiorenal interactions from animal models of CKD and HF and discuss several studies that employed a "double-hit" model to research organ cross talk between the heart and kidneys. ⋯ Variables of renal damage, like glomerulosclerosis and proteinuria, were also further worsened by combined cardiorenal injury. These studies show that target organ cross talk does occur in CRS. These models may be useful for interventional studies in rats.
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Am. J. Physiol. Renal Physiol. · Oct 2012
Interleukin-11 protects against renal ischemia and reperfusion injury.
Renal ischemia reperfusion (IR) injury causes renal tubular necrosis, apoptosis, and inflammation leading to acute and chronic kidney dysfunction. IL-11 is a multifunctional hematopoietic cytokine clinically approved to treat chemotherapy-induced thrombocytopenia. Recent studies suggest that IL-11 also has potent antiapoptotic and antinecrotic properties. ⋯ Moreover, selective HIF-1α inhibitors blocked IL-11-mediated induction of SK1 in HK-2 cells. Finally, HR IL-11 or PEGylated IL-11 failed to protect against renal IR injury in SK1-deficient mice. Together, our data show powerful renal protective effects of exogenous IL-11 against IR injury by reducing necrosis, inflammation, and apoptosis through induction of SK1 via HIF-1α.
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Am. J. Physiol. Renal Physiol. · Oct 2012
Depletion of endogenous kallistatin exacerbates renal and cardiovascular oxidative stress, inflammation, and organ remodeling.
Kallistatin (KS) levels are reduced in the kidney and blood vessels under oxidative stress conditions. To determine the function of endogenous KS in the renal and cardiovascular systems, KS levels were depleted by daily injection of anti-rat KS antibody into DOCA-salt hypertensive rats for 10 days. Administration of anti-KS antibody resulted in reduced KS levels in the circulation but increased levels of serum thiobarbituric acid reactive substances (an indicator of lipid peroxidation) as well as superoxide formation in the aorta. ⋯ In addition, rats receiving anti-KS antibody had enhanced cardiac injury as indicated by cardiomyocyte hypertrophy, inflammation, myofibroblast accumulation, and fibrosis. Renal and cardiac injury caused by endogenous KS depletion was accompanied by increases in the expression of the proinflammatory genes tumor necrosis factor-α and intercellular adhesion molecule-1 and the profibrotic genes collagen I and III, transforming growth factor-β, and tissue inhibitor of metalloproteinase-1. Taken together, these results implicate an important role for endogenous KS in protection against salt-induced renal and cardiovascular injury in rats by suppressing oxidative stress, inflammation, hypertrophy, and fibrosis.
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Am. J. Physiol. Renal Physiol. · Oct 2012
Impact of nitric oxide-mediated vasodilation on outer medullary NaCl transport and oxygenation.
The present study aimed to elucidate the reciprocal interactions between oxygen (O(2)), nitric oxide (NO), and superoxide (O(2)(-)) and their effects on vascular and tubular function in the outer medulla. We expanded our region-based model of transport in the rat outer medulla (Edwards A, Layton AT. Am J Physiol Renal Physiol 301: F979-F996, 2011) to incorporate the effects of NO on descending vasa recta (DVR) diameter and blood flow. ⋯ In addition, our results indicate that the tubulovascular cross talk of NO, that is, the diffusion of NO produced by mTAL epithelia toward adjacent DVR, helps to maintain blood flow and O(2) supply to the interbundle region even under basal conditions. NO also acts to preserve local O(2) availability by inhibiting the rate of active Na(+) transport, thereby reducing the O(2) requirements of mTALs. The dual regulation by NO of oxygen supply and demand is predicted to significantly attenuate the hypoxic effects of angiotensin II.