title: Hyperglycemia abolishes the protective effect of ischemic preconditioning in glomerular endothelial cells in vitro.
abstract: In preclinical investigations, ischemic preconditioning (IPC) protects kidneys from ischemia/reperfusion injury. The direct effects of IPC on glomerular endothelial cells have not been studied in detail. Most investigations of IPC have focused on healthy cells and animals, and it remains unknown whether IPC is renoprotective in the setting of medical comorbidities such as diabetes. In this study, we determined the preventive potential of IPC in healthy glomerular endothelial cell monolayers, and compared these results to monolayers cultured under hyperglycemic conditions. We exposed glomerular endothelial monolayers to 1 h of IPC 24 h prior to oxygen-glucose deprivation (OGD), an in vitro model of ischemia/reperfusion injury. Glomerular endothelial monolayer integrity was assessed by measuring transendothelial electrical resistance, albumin flux, and cell survival. We found that IPC protected healthy but not hyperglycemic glomerular endothelial monolayers from ischemia/reperfusion injury. Furthermore, not only was the protective effect of IPC lost in the setting of hyperglycemia, but IPC was actually deleterious to the integrity of hyperglycemic glomerular endothelial cell monolayers.
authors: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon.
authors: Katie J
authors: KJ
authors: Schenning
authors: Division of Nephrology and Hypertension, Department of Internal Medicine, Oregon Health and Science University, Portland, Oregon Department of Internal Medicine, Portland Veterans Affairs Medical Center, Portland, Oregon.
authors: Sharon
authors: S
authors: Anderson
authors: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon Knight Cardiovascular Institute Oregon Health and Science University, Portland, Oregon.
authors: Nabil J
authors: NJ
authors: Alkayed
authors: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon hutchenm@ohsu.edu.
authors: Michael P
authors: http://orcid.org/0000-0001-8583-1812
authors: MP
authors: Hutchens
keywords: Glomerular endothelial cells; hyperglycemia; ischemic preconditioning; renal ischemia–reperfusion injury