PS-B04-6: FIBROBLAST GROWTH FACTOR 21 - A POTENTIAL NEW TREATMENT FOR HYPERTENSION?

Abstract

Objective: Perivascular adipose tissue (PVAT) is vital in regulation of vascular tone and blood pressure. PVAT function is lost in obesity, contributing to development of hypertension. Fibroblast growth factor-21 (FGF-21) is released by PVAT and has roles in body weight regulation and glucose homeostasis, however, there have been no studies on the direct effect of FGF-21 on vascular tone. Design and method: Wire myography was used to measure the contractility of C57BL/6J mouse second order mesenteric resistance arteries (250 μm) in response to electrical field stimulation (EFS) prior to and following incubation with the FGF-21 analogue PF-05231023 (100 μM) for 30 minutes. PVAT was collected from the entire mesenteric bed and incubated with or without PF-05231023 for 30 minutes before stimulating with EFS. The surrounding supernatant was collected and commercially available adipokine arrays were used to characterise the PVAT secretory profile. Results: PF-05231023 significantly reduced the vasoconstrictor response to EFS in both PVAT intact and PVAT denuded vessels. Using adipokine arrays, PF-05231023 significantly increased adiponectin and leptin secretion from PVAT, in addition to various pro- and anti-inflammatory adipokines. Conclusion: FGF-21 or its analogues could present a promising therapeutic tool to lower blood pressure in hypertension via both direct effects on the vasculature, and by promoting release of other vasodilatory adipokines.