Assessing the Relationship of Angiotensin II Type 1 Receptors with Erythropoietin in a Human Model of Endogenous Angiotensin II Type 1 Receptor Antagonism.

Hypothesis/Introduction: Angiotensin II (Ang II) has been shown to control erythropoietin (EPO) synthesis as Ang II type 1 receptor (AT1R) blockers block Ang-II-induced EPO oversecretion. To further explore the involvement of AT1R in processes controlling EPO levels, plasma EPO and mononuclear cell NADPH oxidase 4 (NOX4) - a NOX family member involved in oxygen sensing, which is a process central to controlling EPO levels - were assessed in Bartter's/Gitelman's syndrome (BS/GS) patients, a human model of endogenous AT1R antagonism and healthy subjects. Heme oxygenase (HO)-1, antioxidant and anti-inflammatory factor related to NOX4 activation, and the relationship of EPO and NOX4 to HO-1 were also assessed. Materials and Methods: EPO was measured by chemiluminescent immunoassay, HO-1 by sandwich immunoassay and NOX4 protein expression by Western blot. Results: EPO was increased in BS/GS patients compared to healthy subjects (7.64 ± 2.47 vs. 5.23 ± 1.07 U/l; p = 0.025), whereas NOX4 did ...