Attenuation of Hypertension and protection of vascular inflammation in hyperaldosteronism: GPER1 as potential therapeutic candidate when MR antagonist is less satisfying?

Abstract

Background: Hyperaldosteronism is an endocrine disorder leading to persistent and severe hypertension. G protein-coupled estrogen receptor 1(GPER1) is regarded as a potential receptor of aldosterone (ALDO).

Objective: This study aimed to investigate the effects of GPER1 on aldosterone (ALDO)-induced hypertension and inflammation in mice.

Methods: GPER1-knockout (KO) and wild-type (WT) C57BL/6j mice were divided into control (CON, normal saline treatment), ALDO (subcutaneous injections of 600 g/kg/d ALDO), and ALDO + eplerenone (EPL) (subcutaneous injections of 600 g/kg/d ALDO and 100 mg/kg/d EPL) groups (n = 5 per group). Fourteen days after drug administration, the heart rate and tail blood pressure of the mice in the different groups were measured. S100A8 and IL-1β protein expression in arterial tissues were detected by western blotting, NLRP3 expression was assessed using immunofluorescence, and CD68 expression was investigated using immunohistochemistry.

Results: GPER1 deficiency alleviated ALDO-induced diastolic blood pressure (P< 0.05). In addition, the protein expression levels of IL-1β, S100A8, and CD68 showed significant decreases in the arterial tissues of GPER1-KO mice after combination treatment with ALDO and EPL (all P < 0.05).

Conclusion: We discovered attenuation of hypertension and vascular inflammation of GPER1 KO mice only on the basis of mineralocorticoid receptor (MR) blocking. Collectively, our study indicates that GPER1 might become a therapeutic target of hyperaldosteronism in controlling the residual risk of cardiovascular disease when MR antagonist alone is not satisfying.

Keywords: Aldosterone; G-protein-coupled estrogen receptor 1; Hypertension; Inflammation.