Journal
KIDNEY INTERNATIONAL
Volume 81, Issue 4, Pages 370-378Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2011.347
Keywords
acute kidney injury; glomerular filtration rate; reactive nitrogen species; renal blood flow; resveratrol; sepsis
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Funding
- National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [F30 DK085705, 10PRE4140065, R01 DK075991-S1, R01 DK075991]
- National Institutes of Health National Center for Research Resources [UL1 RR029884]
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The mortality rate of patients who develop acute kidney injury during sepsis nearly doubles. The effectiveness of therapy is hampered because it is usually initiated only after the onset of symptoms. As renal microvascular failure during sepsis is correlated with the generation of reactive nitrogen species, the therapeutic potential of resveratrol, a polyphenol vasodilator that is also capable of scavenging reactive nitrogen species, was investigated using the cecal ligation and puncture (CLP) murine model of sepsis-induced acute kidney injury. Resveratrol when given at 5.5 h following CLP reversed the decline in cortical capillary perfusion, assessed by intravital microscopy, at 6 h in a dose-dependent manner. Resveratrol produced the greatest improvement in capillary perfusion and increased renal blood flow and the glomerular filtration rate without raising systemic pressure. A single dose at 6 h after CLP was unable to improve renal microcirculation assessed at 18h; however, a second dose at 12h significantly improved microcirculation and decreased the levels of reactive nitrogen species in tubules, while improving renal function. Moreover, resveratrol given at 6, 12, and 18h significantly improved survival. Hence, resveratrol may have a dual mechanism of action to restore the renal microcirculation and scavenge reactive nitrogen species, thus protecting the tubular epithelium even when administered after the onset of sepsis. Kidney International (2012) 81, 370-378; doi:10.1038/ki.2011.347; published online 5 October 2011
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