Kidney Week

Abstract: TH-PO0053

Secretin Signaling and the Renin-Angiotensin-Aldosterone System

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

• Andersen, Jesper Frank, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Jesper Frank Andersen, MD

• Trans, Laura Woidemann, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Laura Woidemann Trans, MS

• Leipziger, Jens G., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Jens G. Leipziger, MD, DrMed

• Berg, Peder, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Peder Berg, MD, PhD

Background

The renin-angiotensin-aldosterone system is activated through several different pathways in response to loss of circulatory volume. Activation increases renal electrolyte and water reabsorption along with bicarbonate excretion mediated through the Cl^-/HCO₃^- antiporter pendrin.
Secretin, a hormone typically associated with the gastrointestinal system, also increases pendrin-dependent base excretion. Additional evidence suggests that secretin signaling affects both AVP and aldosterone release and that the secretin receptor (SCTR) and angiotensin II receptor interact functionally.
This study aimed to investigate how loss of secretin signaling alters the activation of the renin-angiotensin-aldosterone system and the cardiovascular and renal consequences hereof.

Methods

Following cardiovascular and renal phenotyping, SCTR WT and KO mice (10+10, C57BL/6 background) were subjected to continuous angiotensin II infusion via mini-osmotic pumps (750 ng/kg/min) for 28 days. At termination, similar phenotyping was repeated. The mice were then anesthetized (i.p. ketamine/xylazine) and kidney tissue and plasma harvested. Western blots for relevant transporters were performed on kidney lysates. Additionally, fibrosis staining and immunohistochemistry were performed on the harvested tissue.

Results

Angiotensin II induced marked hypertension in both KO and WT mice and decreased GFR. WTs developed significantly more albuminuria. Urinary pH increased significantly in WTs while no effect was seen in the KOs. WTs had significantly higher fractional sodium excretion than KOs. Furthermore, WTs had a greater upregulation of both ENaC and pendrin protein levels compared with KOs, while both genotypes exhibited increased NCC activation. Further analyses of aldosterone levels and ADH activation are pending.

Conclusion

Defective secretin signaling in SCTR KO mice blunts the systemic and renal effects of angiotensin II. Together, these data expand on the importance of functional secretin signaling in the activation of the renin-angiotensin-aldosterone system.