Article activity feed

  1. Evaluation Summary:

    This paper extends our understanding of blood flow regulation in the ischemic kidney and adds to a growing body of literature on the role played by pericyte contraction in the aftermath of ischemia/reperfusion (much of it based on the CNS microvasculature), and the potential of capillary pericytes as therapeutic targets in mitigating ischemia/reperfusion injury. This is an important study which should be of interest to a wide variety of investigators in vascular and renal biology.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their names with the authors.)

    Was this evaluation helpful?
  2. Joint Public Review:

    In this manuscript, Freitas and Attwell use a rat model of renal ischemia and reperfusion to investigate the cellular and molecular basis of acute kidney injury that follows renal ischemia/reperfusion, such as occurs in certain clinical settings, including cardiac surgery, renal transplantation and severe hemorrhage. They found that the long-lasting "no-flow" phenomenon that develops under these conditions is attributable to contraction of pericytes in descending vasa recta and peritubular capillaries, without the involvement of glomerular arterioles. Using a pharmacological approach, they further demonstrated that perfusion during the reperfusion phase was normalized in the cortex and increased relative to controls in the medulla by the selective RhoA/Rho kinase (ROCK) inhibitor, hydroxyfasudil (HF). The authors conclude that ROCK-dependent contraction of capillary pericytes is responsible for the observed long-lasting decrease in blood flow in the kidney upon ischemia/reperfusion.

    Support for capillary pericyte contraction is largely descriptive - imaging in kidney slices from NG2-DsRed mice perfused with a FITC-albumen/gelatin solution showing reduced capillary diameter near NG2-labeled cells combined with a quantitative analysis of the distribution of blockage-pericyte distances. Data obtained using HF provides additional indirect support for the centrality of pericyte contraction/relaxation, showing that HF increases capillary blood flow, increases capillary diameter in the vicinity of pericytes, and does not affect the diameter of glomerular arterioles.

    Was this evaluation helpful?