Hydralazine Lowers Serum Triglyceride Levels by Enhancing Farnesoid X Receptor Signaling and Adipose Triglyceride Lipase Expression : In Vivo Evidence from Male Spontaneously Hypertensive Rats

Background : Hydralazine (HYD) is a vasodilator widely used for the management of hypertension and related conditions, including heart failure and eclampsia. While previous studies have shown that HYD mitigates hepatic steatofibrosis induced by a high-fat, high-cholesterol diet in spontaneously hypertensive rats (SHRs), its precise effects on lipid metabolism remain unclear. This study investigated the impact of HYD on serum and hepatic lipid profiles and explored potential underlying mechanisms. Methods : Male SHRs received HYD via drinking water (60 mg/L) for either four or ten weeks, followed by analyses of clinical parameters and hepatic gene expression. Results : HYD significantly reduced serum triglyceride (TG) levels at both time points. In the liver, HYD markedly upregulated small heterodimer partner, a target gene of the farnesoid X receptor (FXR), as well as adipose triglyceride lipase (ATGL). After ten weeks of HYD treatment, the expression of peroxisome proliferatoractivated receptor α was also significantly elevated, coinciding with reduced serum TG levels. Conclusion : These findings suggest that HYD lowers lipid levels primarily by activating the FXR signaling pathway and enhancing ATGL expression, highlighting a novel pharmacological role of HYD in lipid metabolism.