Development of Oxidative Stress in the Peritubular Capillary Microenvironment Mediates Sepsis-Induced Renal Microcirculatory Failure and Acute Kidney Injury

• DOI: 10.1016/j.ajpath.2011.10.011
• Publication Date: 2011-11-29T21:23:32Z
• Authors: Zhen Wang; Joseph H. Holthoff; Kathryn A. Seely; Elina Pathak; Horace J. Spencer; Neriman Gokden; Philip R. Mayeux
• Keywords: Peritubular capillaries

Acute kidney injury is a frequent and serious complication of sepsis. To better understand the development sepsis-induced acute injury, we performed first time-dependent studies to document changes in renal hemodynamics oxidant generation peritubular microenvironment using murine cecal ligation puncture (CLP) model CLP caused an increase capillary permeability at 2 hours, followed by decreases mean arterial pressure, blood flow (RBF), perfusion 4 which were sustained through 18 hours. The decline hemodynamic parameters was associated with hypoxia decrease glomerular filtration rate. role oxidants assessed superoxide dismutase mimetic/peroxynitrite scavenger MnTMPyP [Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin]. At 10 mg/kg administered 6 hours after CLP, did not alter but blocked peroxynitrite generation, reversed RBF, perfusion, rate, preserved tubular architecture, increased 48-hour survival. However, prevent or RBF suggests that these early events are mediated oxidants. These data demonstrate occur sepsis targeting later can break cycle enable microcirculation function recover.