Oxidative stress upregulates renal Angiotensin II type I receptors via activation of transcription factor nuclear factor‐kappaB

Abstract

Regulation of redox homeostasis is associated with normal functioning of cells, whereas oxidative stress is seen with various cardiovascular disorders like hypertension. Angiotensin II (Ang II), acting via Ang II type I (AT1) receptors, has known effects on the renal proximal tubular sodium transport, thus plays an important role in regulating blood pressure. Oxidative stress is also known to activate redox sensitive transcription factor NF‐kappaB and evidences indicate that AT1 receptor gene posses binding site for this transcription factor. Herein, we aim to investigate if oxidative stress upregulates renal AT1 receptors through NF‐kappaB activation. Human proximal tubular (HK‐2) cells were incubated with a pro oxidant L‐buthionine sulfoximine (BSO), an inhibitor of glutathione, for 48 hrs.ResultsCompared to control, there was an increase in levels of protein nitrotyrosination indicating oxidative stress in BSO treated HK‐2 cells. There was also activation of NF‐kappaB, upregulation of AT1 receptor protein, and increased Ang II‐induced Ca2+ signaling. Furthermore, treatment with pyrrolidine dithiocarbamate, a NF‐kappaB inihibitor, blocked NF‐kappaB activation, abolished AT1 receptor upregulation and exaggerated Ang II induced Ca2+ signaling.ConclusionThese results suggest that oxidative stress upregulates renal AT1 receptors via activation of transcription factor NF‐kappaB.Grant: AHA‐SDG‐0835428N