title: Angiotensin II receptors and peritoneal dialysis-induced peritoneal fibrosis.
abstract: The vasoactive hormone angiotensin II initiates its major hemodynamic effects through interaction with AT1 receptors, a member of the class of G protein-coupled receptors. Acting through its AT1R, angiotensin II regulates blood pressure and renal salt and water balance. Recent evidence points to additional pathological influences of activation of AT1R, in particular inflammation, fibrosis and atherosclerosis. The transcription factor nuclear factor κB, a key mediator in inflammation and atherosclerosis, can be activated by angiotensin II through a mechanism that may involve arrestin-dependent AT1 receptor internalization. Peritoneal dialysis is a therapeutic modality for treating patients with end-stage kidney disease. The effectiveness of peritoneal dialysis at removing waste from the circulation is compromised over time as a consequence of peritoneal dialysis-induced peritoneal fibrosis. The non-physiological dialysis solution used in peritoneal dialysis, i.e. highly concentrated, hyperosmotic glucose, acidic pH as well as large volumes infused into the peritoneal cavity, contributes to the development of fibrosis. Numerous trials have been conducted altering certain components of the peritoneal dialysis fluid in hopes of preventing or delaying the fibrotic response with limited success. We hypothesize that structural activation of AT1R by hyperosmotic peritoneal dialysis fluid activates the internalization process and subsequent signaling through the transcription factor nuclear factor κB, resulting in the generation of pro-fibrotic/pro-inflammatory mediators producing peritoneal fibrosis.
authors.affiliation: Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States. Electronic address: morinelt@musc.edu.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Morinelli
authors.affiliation: Division of Endocrinology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, United States.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Luttrell
authors.affiliation: Division of Endocrinology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Strungs
authors.affiliation: Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, United States.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ullian
mesh_terms: D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*
chemical_list: D011945:Receptors, Angiotensin
keywords: AT1R; Angiotensin II; Arrestin; Fibrosis; Peritoneal mesothelial cells