Fibroblast Growth Factor 21 Ameliorates Endothelin I-Induced Hypertension Partly Through PPAR γ Pathway

Fibroblast growth factor 21 (FGF21) is a metabolic regulator with a wide range of biological functions. Although previous studies have shown the potential of FGF21 to ameliorate hypertension, the precise mechanisms of action remain unclear. Here, we present a hypertension model of ET-1-induced in rats. FGF21 improved RAAS homeostasis in hypertensive rats by reducing plasma renin activity (PRA), Angiotensin II (Ang II) and Aldosterone (ALD) levels. In addition, FGF21 markedly reversed vascular inflammation by reducing the expression of TNF-α, IL-1, IL-6 and IL-8 in hypertensive rats. Treatment with FGF21 decreased total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) levels, while increased high density lipoprotein (HDL) levels. To explore the mechanism, we measured the expression of PPARγ in rats. Interestingly, treatment with FGF21 promoted PPAR γ expression, thereby inhibiting the expression of ET-1 and VCAM-1, which in turn inhibited the expression of inflammatory factors in hypertensive rats. PPAR γ further regulated hypertension by inhibiting SGLT-2 expression. In conclusion, we uncovered a role for FGF21 ameliorates ET-1 induced hypertension by mediating ET-1, VCAM-1 and SGLT-2 axis through PPAR γ pathway.