# Cerebrospinal fluid proteomic analysis of long-term antihypertensive treatment with amlodipine and atenolol in hypertensive rats

## TL;DR

This study examines how long-term blood pressure medications affect brain fluid proteins in hypertensive rats, revealing distinct effects on brain-related processes.

## Contribution

The study provides novel insights into how amlodipine and atenolol affect the cerebrospinal fluid proteome in hypertensive rats.

## Key findings

- Hypertension altered central nervous system development, inflammation, and coagulation-related proteins in CSF.
- Amlodipine affected gas transport proteins, while atenolol influenced complement and coagulation cascade proteins.
- The two treatments altered pathways related to cell adhesion, CNS development, and vascular development.

## Abstract

Midlife hypertension has been identified as a risk factor for the development of dementia, however, the underlying mechanism of this correlation remains unclear. In this study, we analyzed cerebrospinal fluid (CSF) samples from spontaneously hypertensive rats (SHR) that had been treated with either amlodipine or atenolol for one year and compared these to normotensive Wistar Kyoto rats (WKY). Mass spectrometry-based proteomic analysis of the CSF samples was conducted to identify both the impact of hypertension as well as antihypertensive treatment on CSF proteomics. Both systolic and diastolic blood pressure were increased in hypertensive rats, and both medications lowered blood pressure compared to untreated SHR rats. The analysis of the CSF proteome revealed that hypertension resulted in alterations to processes associated with the development of the central nervous system, inflammation and blood coagulation. The latter included proteins such as YKL-40, KNG1, DAG1, and members of the Serpin family. Amlodipine treatment resulted in changes to proteins involved in gas transport (including CA2, HBB, and HBA1), whereas atenolol treatment led to changes in the complement and coagulation cascade (including CFH, KNG1, APOE, and AHSG). A comparison of the two antihypertensive treatments revealed alterations in pathways associated with cell adhesion, central nervous system development, and vascular development. These findings show that hypertension and long-term treatment with antihypertensive medications elicit distinct effects on the CSF proteome.

The online version contains supplementary material available at 10.1038/s41598-025-21450-3.