A Pathophysiologic Mechanism for the Treatment of Salt-Sensitive Hypertension and Heart Failure: The Role of β-Arrestins.

Abstract

This paper aims to introduce a new treatment strategy for salt-sensitive hypertension and heart failure (HF). Hypertension is very common and a major risk factor for cardiovascular disease, coronary heart disease, HF, and death. Yet neither hypertension nor HF are well controlled with the existing medications. Therefore, new means for their control should be pursued. Recently, β-arrestins have been investigated and shown to have beneficial effects in both hypertension and HF. β-Arrestins are a family of intracellular signaling proteins that play a role in the regulation of the G-protein-coupled receptors. The angiotensin II (Ang II) type 1 receptor (AT1R) is also a G-protein-coupled receptor mediating the adverse cardiovascular effects of Ang II. An agonist that activates the β-arrestin pathway downstream of the AT1R, such as TRV027, could act as a therapeutic agent by blocking the adverse effects of Ang II. Yet at present, the therapeutic effects of TRV027 are weak and short lasting. Therefore, there is an urgent need for the development of more effective and long-lasting TRV027 analogs. A review of the recent literature from 2019 to 2024 has disclosed that β-arrestins do possess beneficial effects in lowering hypertension and treating HF.