Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury
Daniel E Leisman, Tiago D Fernandes, Vanesa Bijol, Mabel N Abraham, Jake R Lehman, Matthew D Taylor, Christine Capone, Omar Yaipan, Rinaldo Bellomo, Clifford S Deutschman
Kidney International | ELSEVIER SCIENCE INC | Published : 2021
In sepsis-induced acute kidney injury, kidney blood flow may increase despite decreased glomerular filtration. Normally, angiotensin-II reduces kidney blood flow to maintain filtration. We hypothesized that sepsis reduces angiotensin type-1 receptor (AT1R) expression to account for this observation and tested this hypothesis in a patient case-control study and studies in mice. Seventy-three mice underwent cecal ligation and puncture (a sepsis model) or sham operation. Additionally, 94 septic mice received losartan (selective AT1R antagonist), angiotensin II without or with losartan, or vehicle. Cumulative urine output, kidney blood flow, blood urea nitrogen, and creatinine were measured. AT1..View full abstract
We thank Richard Hotchkiss, MD, for providing human sepsis tissue specimens; Joaquin Cagliani, MD, for providing tissue samples from mice subjected to a model of hemorrhagic shock; and Lahkmir Chawla, MD, and John Kellum, MD, PhD, for their comments on preliminary results from these experiments. MDT received grant support (NIGMS K08GM132794), and CSD received grant support (R01GM121102).