The potential function of distal cerebrospinal fluid-contacting nucleus (
dCSF-CNs) in
chronic kidney disease (CKD) development is poorly understood. We hypothesized that
dCSF-CNs might affect the renin-angiotensin system (RAS) in kidney injury progression, with
dCSF-CNs ablation potentially alleviating local RAS and renal
fibrosis in rats after five-sixths
nephrectomy (5/6Nx). Part of rats were randomly administered artificial cerebrospinal fluid (aCSF) intracerebroventricularly (icv), followed by 5/6Nx or
sham operation; and other part of rats were administered
Cholera toxin B subunit conjugated with
saporin (CB-SAP) for
dCSF-CNs lesion before 5/6Nx. The effect of CB-SAP on
dCSF-CNs ablation was confirmed by double immunofluorescence staining. RAS component, NOX2 and c-fos levels in the subfornical organ (SFO), hypothalamic paraventricular nucleus (PVN) and hippocampus, as well as
tyrosine hydroxylase (TH) and c-fos positive cells in rostral ventrolateral medulla (RVLM) were assessed. Next, the levels of RAS components (
angiotensinogen [AGT],
angiotensin-converting enzyme [ACE], Ang II type 1 receptor [AT1R],
angiotensin-converting enzyme 2 [ACE2], and Mas receptor),
NADPH oxidases (NOX2 and
catalase), inflammatory
cytokines (
monocyte chemotactic protein 1 [MCP-1] and IL-6), and fibrotic factors (
fibronectin and
collagen I) were assessed. Less CB-labeled neurons were found in
dCSF-CNs of CB-SAP-treated rats compared with 5/6Nx animals. Meanwhile, CB-SAP downregulated AGT, Ang II, AT1R, NOX2,
catalase, MCP-1,
IL-6,
fibronectin, and
collagen I, and upregulated ACE2 and Mas receptor, compared with CKD rats. More TH and c-fos positive cells were found in RVLM of 5/6Nx rats but the number decreased after
dCSF-CNs ablation. Targeted
dCSF-CNs ablation could alleviate renal
inflammation and
fibrosis in chronic kidney injury by inhibiting cerebral and renal RAS/
NADPH oxidase.