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November 30, 2020Hypertension26 citationsOpen Access

β-Arrestin–Biased Agonist Targeting the Brain AT 1 R (Angiotensin II Type 1 Receptor) Increases Aversion to Saline and Lowers Blood Pressure in Deoxycorticosterone Acetate–Salt Hypertension

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Why the study?

Does intracerebroventricular TRV027 lower blood pressure and alter fluid intake in a mouse model of DOCA-salt hypertension?

Population

Mice subjected to deoxycorticosterone acetate (DOCA)-salt hypertension, and a neuronal cell line.

Comparison

Intracerebroventricular administration of… vs Intracerebroventricular vehicle or losartan…

Design

Preclinical

Key result

Central administration of the β-arrestin-biased agonist TRV027 increased aversion to saline and significantly reduced blood pressure and heart rate in mice with DOCA-salt hypertension.

Authors

MZMario ZanatyFSFernando A. C. SearaPNPablo Nakagawa

Discussion

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Overview

May support central β-arrestin-biased AT1R agonism in salt-sensitive hypertension; leaves open translation to humans.

Structured PICO

Does intracerebroventricular TRV027 lower blood pressure and alter fluid intake in a mouse model of DOCA-salt hypertension?

P
Population
Mice subjected to deoxycorticosterone acetate (DOCA)-salt hypertension, and a neuronal cell line.
I
Intervention
Intracerebroventricular administration of TRV120027 (TRV027), an AT1R-biased agonist (chronic infusion or acute injection).
C
Comparator
Intracerebroventricular vehicle or losartan. Sham mice received vehicle without DOCA.
O
Outcome
Fluid intake (relative intake of water versus various saline solutions) and blood pressure/heart rate.surrogate

Central administration of the AT1R β-arrestin-biased agonist TRV027 increases saline aversion and lowers blood pressure in a mouse model of salt-sensitive hypertension, suggesting a potential therapeutic role for selective AT1R β-arrestin pathway activation.

Cite This Study

Zanaty et al. (2020) studied Deoxycorticosterone acetate (DOCA)-salt hypertension. TRV120027 (TRV027) vs. Vehicle or losartan was evaluated on Relative intake of water versus saline solutions and blood pressure. Central administration of the β-arrestin-biased agonist TRV027 increased aversion to saline and significantly reduced blood pressure and heart rate in mice with DOCA-salt hypertension.

synapsesocial.com/papers/6a1c89f70e2acd31eb2fda8ahttps://doi.org/10.1161/hypertensionaha.120.15793
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