Simultaneous adrenal and cardiac g-protein-coupled receptor-gβγ inhibition halts heart failure progression.

ABSTRACT:

Objectives

The authors propose simultaneous inhibition of Gβγ signaling in the heart and the adrenal gland as a novel therapeutic approach for heart failure (HF).

Background

Elevated sympathetic nervous system activity is a salient characteristic of HF progression. It causes pathologic desensitization of β-adrenergic receptors (β-AR), facilitated predominantly through Gβγ-mediated signaling. The adrenal glands are key contributors to the chronically elevated plasma catecholamine levels observed in HF, where adrenal α2-AR feedback inhibitory function is impaired also through Gβγ-mediated signaling.

Methods

We investigated the efficacy of a small molecule Gβγ inhibitor, gallein, in a clinically relevant, pressure-overload model of HF.

Results

Daily gallein treatm

SUBMITTER: Kamal FA 

PROVIDER: S-EPMC4083020 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature