Resveratrol improves renal blood flow and microcirculation in the kidney during experimental septic shock in mice

Septic shock affects approximately 750,000 patients annually in the US. In patients who develop acute kidney injury (AKI) during sepsis the mortality rate nearly doubles to 75%. Thus, there is a pressing need for the development of therapeutic approaches to treat sepsis‐induced AKI. We have previously shown decreased capillary perfusion and peroxynitrite (PXN) generation in the kidneys of septic mice. We have also recently published that the polyphenol resveratrol (RSV) can act as a direct scavenger of PXN. Reports of the cardiovascular effects of RSV led us to hypothesize that RSV may protect the renal microcirculation during sepsis. Cecal ligation and puncture (CLP) was used to induce sepsis in aged (40 weeks) mice. At 6h post CLP (prior to PXN generation) blood pressure, renal blood flow and renal capillary perfusion are all decreased. At 5.5h following CLP, mice were treated with RSV (3, 10, 30, or 100 mg/kg) and evaluated at 6h. Using intravital video microscopy we show that RSV restored renal capillary perfusion, red blood cell velocity, and volumetric blood flow to sham levels. RSV also increased renal blood flow without raising blood pressure. These data suggest that RSV may have a dual mechanism of action to restore the renal microcirculation and protect against development of sepsis‐induced AKI even when administered after the onset of sepsis. Supported by NIH F30 DK085705 (JHH) and DK075991 (PRM).