Methyl palmitate is the perivascular adipose tissue‐derived relaxing factor

Abstract

The perivascular adipose tissue (PVAT)‐derived relaxing factor (PVATRF) is known to significantly regulate the vascular smooth muscle tone. Its chemical nature, however, remains unknown. We determined whether methyl palmitate or palmitic acid methyl ester (PAME) was the PVATRF. Release of PVATRF and PAME from aortic PVAT preparations of Wistar Kyoto rats was estimated using superfusion bioassay cascade technique and gas chromatography/mass spectrometry (GC/MS). The PVATRF and PAME were spontaneously and calcium‐dependently released from PVAT preparations. Both releases were inhibited by 4‐aminopyridine (2 mM) and tetraethylammonium (TEA) at 10 mM, but were not affected by TEA at 3 mM, glibenclamide (3 μM) or iberiotoxin (100 nM). Aortic vasorelaxations induced by PVATRF‐ and PAME‐containing Krebs' solutions were not affected after heating at 70°C, and were equally attenuated following hexane extractions. Culture mediums of differentiated adipocytes, but not those of fibroblasts, contained significant PAME and caused aortic vasorelaxation. These results indicate that PAME and PVATRF share similar characteristics in biochemistry and pharmacology. It is concluded that PAME is the PVATRF, causing aortic vasorelaxation by opening voltage‐dependent K+ channels on the smooth muscle cells (Supported by NSC, Tzu Chi Foundation & TCU).