Inhibition of Rho-kinase attenuates endothelial–leukocyte interaction during ischemia–reperfusion injury
Year: 2012
Type: article
Abstract: Resuscitation from hemorrhagic shock induces endothelial dysfunction and activates inflammatory cascades leading to organ damage. Following restoration of blood flow to ischemic vascular beds, leukocyte-endothelium interactions leading to leukocyte infiltration into the vascular wall occur very early due, in part, to the loss of endothelium-derived nitric oxide (NO). The mechanism by which ischemia-reperfusion injury impairs endothelium-derived NO is not completely understood. We hypothesized that inhibition of Rho-kinase could exert beneficial effects following hemorrhagic shock by preserving endothelial function and attenuating leukocyte trafficking in the microcirculation. Using intravital microscopy, we found that resuscitation from hemorrhage acutely increased the number of rolling and adherent leukocytes in the mouse splanchnic microcirculation. Treatment of mice with the Rho-kinase inhibitor fasudil, markedly attenuated leukocyte-endothelium interaction in response to hemorrhage/reinfusion. The beneficial effect of fasudil was not observed in endothelial nitric oxide synthase (eNOS)(-/-) mice. In conclusion, inhibition of Rho-kinase prevents inflammatory leukocyte trafficking in the microcirculation via an eNOS-dependent mechanism. Our data support a role for Rho-kinase inhibitors in the treatment of ischemia-reperfusion injury.
Source: Vascular Medicine
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1206115150, Novel Signaling Pathways in Ischemic Stroke, G2909016103, Endothelial Akt in Vascular Injury, Rho Kinase and Airway Hyperresponsiveness, G6432216607, Activation of eNOS by Steroid Hormones, Lipoproteins Effect on G Protein Function, Role of PI3-Kinase in Estrogen-induced eNOS Activation, G7667615797, ROCK and Obesity, Arterial Dysfunction: Basic and Clinical Mechanisms, Interdepartmental Stroke Program
OpenAlex ID: W2113807313