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

Area of Science:

• Cardiovascular Research
• Nephrology
• Endocrinology

Background:

• Hypertension, linked to high sodium intake, is a global health issue.
• Omentin-1, an adipokine, has anti-inflammatory and antioxidant roles, but its effect on salt-sensitive hypertension is unknown.

Purpose of the Study:

• To investigate the blood pressure-lowering and kidney-protective effects of omentin-1.
• To elucidate the underlying molecular mechanisms in a rat model of deoxycorticosterone acetate (DOCA)-salt hypertension.

Main Methods:

• Utilized a DOCA-salt rat model to induce hypertension.
• Assessed the impact of omentin-1 overexpression on blood pressure, renal function markers (serum creatinine, BUN), renal fibrosis, and histopathology.
• Investigated the expression of angiotensin II type 1 receptor (AT1R) and G protein-coupled receptor kinase 4 (GRK4) in renal tissue.
• Explored the role of the reactive oxygen species (ROS)/c-Myc signaling pathway in mediating omentin-1's effects.

Main Results:

• Omentin-1 overexpression significantly reduced blood pressure and improved renal function in hypertensive rats.
• Omentin-1 decreased renal fibrosis and improved kidney histopathology.
• Omentin-1 downregulated renal AT1R and GRK4 expression via the ROS/c-Myc pathway.
• GRK4 overexpression counteracted the beneficial effects of omentin-1, confirming its role as a mediator.

Conclusions:

• Omentin-1 exhibits significant antihypertensive and renal protective effects in salt-sensitive hypertension.
• The mechanism involves the suppression of the ROS/c-Myc/GRK4/AT1R signaling axis.
• Omentin-1 represents a promising therapeutic target for managing salt-sensitive hypertension and associated kidney damage.