Omentin-1 attenuates salt-sensitive hypertension via GRK4/AT1R downregulation mediated by the ROS/c-Myc pathway.

Hypertension, a major risk factor for cardiovascular diseases, is closely associated with excessive sodium intake and affects millions globally. Omentin-1, an adipokine with anti-inflammatory and antioxidant properties, has been implicated in blood pressure regulation, but its role in salt-sensitive hypertension remains unclear. This study investigated the antihypertensive and renal protective effects of omentin-1 in a deoxycorticosterone acetate (DOCA)-salt hypertensive rat model. We demonstrated that Omentin-1 overexpression significantly reduced blood pressure and attenuated renal dysfunction in DOCA-salt hypertensive rats, as evidenced by decreased serum creatinine (Scr) and blood urea nitrogen (BUN) levels, reduced renal fibrosis, and improved histopathological scores. Mechanistically, Omentin-1 downregulated angiotensin II type 1 receptor (AT1R) expression in the kidney, which was associated with reduced G protein-coupled receptor kinase 4 (GRK4) levels. Further analysis revealed that omentin-1 suppressed GRK4 expression via the reactive oxygen species (ROS)/c-Myc signaling pathway. Overexpression of GRK4 abolished the antihypertensive and renal protective effects of omentin-1, confirming GRK4 as a key mediator in this process. These findings highlight omentin-1 as a potential therapeutic target for salt-sensitive hypertension, offering dual benefits in blood pressure reduction and renal protection through the ROS/c-Myc/GRK4/AT1R axis.