title: Role of perivascular adipose tissue-derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension.
abstract: BACKGROUND
  Perivascular adipose tissue (PVAT)-derived relaxing factor (PVATRF) significantly regulates vascular tone. Its chemical nature remains unknown. We determined whether palmitic acid methyl ester (PAME) was the PVATRF and whether its release and/or vasorelaxing activity decreased in hypertension.
  
  
  RESULTS
  Using superfusion bioassay cascade technique, tissue bath myography, and gas chromatography/mass spectrometry, we determined PVATRF and PAME release from aortic PVAT preparations of Wistar Kyoto rats and spontaneously hypertensive rats. The PVAT of Wistar Kyoto rats spontaneously and calcium dependently released PVATRF and PAME. Both induced aortic vasorelaxations, which were inhibited by 4-aminopyridine (2 mmol/L) and tetraethylammonium 5 and 10 mmol/L but were not affected by tetraethylammonium 1 or 3 mmol/L, glibenclamide (3 μmol/L), or iberiotoxin (100 nmol/L). Aortic vasorelaxations induced by PVATRF- and PAME-containing Krebs solutions were not affected after heating at 70°C but were equally attenuated after hexane extractions. Culture mediums of differentiated adipocytes, but not those of fibroblasts, contained significant PAME and caused aortic vasorelaxation. The PVAT of spontaneously hypertensive rats released significantly less PVATRF and PAME with an increased release of angiotensin II. In addition, PAME-induced relaxation of spontaneously hypertensive rats aortic smooth muscle diminished drastically, which was ameliorated significantly by losartan.
  
  
  CONCLUSIONS
  We found that PAME is the PVATRF, causing vasorelaxation by opening voltage-dependent K+ channels on smooth muscle cells. Diminished PAME release and its vasorelaxing activity and increased release of angiotensin II in the PVAT suggest a noble role of PVAT in pathogenesis of hypertension. The antihypertensive effect of losartan is attributed partly to its reversing diminished PAME-induced vasorelaxation.
authors.affiliation: Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Yuan-Chieh
authors.initials: YC
authors.lastname: Lee
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Chang
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Chiang
authors.forename: Chin-Hung
authors.initials: CH
authors.lastname: Liu
authors.forename: Jih-I
authors.initials: JI
authors.lastname: Yeh
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Chen
authors.forename: Po-Yi
authors.initials: PY
authors.lastname: Chen
authors.forename: Jon-Son
authors.initials: JS
authors.lastname: Kuo
authors.forename: Tony J F
authors.initials: TJ
authors.lastname: Lee
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010168:Palmitates / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism*
chemical_list: D010168:Palmitates; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D000804:Angiotensin II; D019789:Tetraethylammonium; C064719:iberiotoxin; D015761:4-Aminopyridine; C019012:methyl palmitate; D019808:Losartan; D005905:Glyburide; D002118:Calcium