The Role of Cell Swelling in Ischemic Renal Damage and the Protective Effect of Hypertonic Solute

Abstract

A B S T R A C T The failure of blood flow to return to the kidney following a transient period of ischemia has long been recognized. The cause of this "no-reflow" has been investigated in the rat after a transient period of total obstruction of the renal arteries. The vascular pattern of the kidneys as visualized with silicone rubber injection shows a diffuse patchy ischemia throughout the kidney, which persists after release of the obstructed renal artery. Electron microscopic studies of ischemic kidneys showed that all cellular elements were swollen and limiting the available vascular space. Functional studies revealed an increase in plasma urea nitrogen and creatinine after 1 hr or longer ischemic periods. The ischemia, cell swelling, "no-reflow," and subsequent renal dysfunction occurring after obstruction to the renal arteries were corrected by the administration of hypertonic mannitol, but were unaffected by an equivalent expansion of the extracellular fluid volume either with isotonic saline or isotonic mannitol, showing that the osmotic effect was primary. The hypothesis is presented that ischemic swelling of cells may occlude small blood vessels so that recirculation does not resume even after the initial cause of the ischemia is no longer present; solutes which do not penetrate cell membranes are able to shrink swollen cells, increase the available vascular space and thus permit reflow of blood to the ischemic organ.

The role of microvesicles in tissue repair

“…One advantage of using MVs rather than the MSCs themselves is to avoid possible long-term maldifferentiation of engrafted cells or tumor generation. 40 Although ischemic and nephrotoxic insults are believed to predominantly target the tubular epithelium, it has become increasingly clear that renal endothelial cells in AKI undergo early damage and swelling, 41 causing narrowing of the vascular lumen, followed by impaired microvasculature perfusion. 42 The most important consequence of this "no-reflow" phenomenon is a delayed functional recovery of the damaged kidney due to prolonged hypoperfusion.…”

Hematopoietic MicroRNA-126 Protects against Renal Ischemia/Reperfusion Injury by Promoting Vascular Integrity

“…peritubular capillary network is rapidly impaired as a consequence of endothelial cell (EC) swelling, 5 impaired vasorelaxation, 6 and increased leukocyte adhesion. 7 In addition, microvascular destabilization initiated by the loss of EC-EC interaction 8 and EC-pericyte interactions can lead to significant reductions in peritubular capillary density due to microvascular rarefaction.…”

Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice

“…As successful reperfusion after ischemia can improve renal tissue viability and recovery, there is an urgent need to better understand and characterize molecular pathways that control renal blood flow in the postischemic period. Indeed, persistent microvascular dysfunction has been implicated in preventing capillary reflow despite successful opening of the arterial blood supply in several models of ischemia and reperfusion (24,36), including the kidneys (37). Surprisingly, the present studies on adenosine transporters directed us toward a critical contribution of extracellular adenosine to the prevention of microvascular dysfunction following ischemic AKI.…”