# An Optimized Chickpea Protein Hydrolysate Exerts Long-Term Antihypertensive Effects and Upregulates ACE2 and Mas1 Gene Expression in Spontaneously Hypertensive Rats

## TL;DR

A chickpea protein supplement lowers blood pressure in rats and activates genes linked to blood pressure regulation.

## Contribution

This study demonstrates the long-term antihypertensive effects and molecular mechanisms of an optimized chickpea protein hydrolysate.

## Key findings

- Daily supplementation with OCPH significantly reduced systolic, diastolic, and mean blood pressure in hypertensive rats.
- OCPH increased ACE2 and Mas1 gene expression in the kidneys, suggesting activation of a blood pressure-lowering pathway.
- ACE2 mRNA levels were negatively correlated with blood pressure, supporting its role in the observed effects.

## Abstract

Chickpea protein hydrolysates have antihypertensive potential. However, neither the effect of their daily consumption on blood pressure (BP) nor their potential antihypertensive mechanisms has been evaluated. Thus, both the antihypertensive effect of an optimized chickpea protein hydrolysate (OCPH) and its potential mechanisms were assessed in spontaneously hypertensive rats. OCPH (50 mg/kg of body weight) was supplemented daily (5 weeks), BP levels were measured, and mRNA relative levels (angiotensin-converting enzyme-I (ACE1), renin, AT1R receptor, ACE2 and Mas1) in the kidneys were determined. BP (systolic, diastolic, and mean) levels were lowered after five days of OCPH supplementation (p < 0.05 vs. control group) and the hypotensive effect was up to −39.80 mmHg (p < 0.05). Furthermore, the supplementation increased ACE2 (67.30%) and Mas1 (61.1%) mRNA levels (p < 0.05 vs. control group). ACE1, renin and AT1R receptor mRNA levels were similar between groups (p > 0.05). A negative correlation of ACE2 mRNA levels with BP was found (p < 0.05). The findings support that OCPH activates the ACE2/Ang-(1–7)/Mas1 pathway of the renin–angiotensin–aldosterone system, maintaining a reduction in BP after daily supplementation. Further studies to evaluate the potential of the OCPH for functional food and nutraceutical development are justified.