title: The mechanisms of propofol-induced vascular relaxation and modulation by perivascular adipose tissue and endothelium.
abstract: BACKGROUND
  Propofol causes hypotension due to relaxation of vascular smooth muscle cells through its direct or indirect vasodilator effects. Perivascular adipose tissue (PVAT) and endothelium attenuate vascular contraction, and the function of PVAT is altered in hypertension and diabetes. Whether PVAT affects the action of anesthetics on vascular function is unknown. We studied the mechanisms of propofol-induced relaxation in relation to the involvement of PVAT and endothelium.
  
  
  METHODS
  Thoracic aortic rings from Wistar rats were prepared with or without PVAT (PVAT+ and PVAT-), intact endothelium (E+), or both, or with the endothelium removed (E-) for functional studies.
  
  
  RESULTS
  In phenylephrine precontracted vessels, propofol-induced relaxation was highest with both PVAT and E+ and lowest in vessels denuded of both PVAT and endothelium. Propofol-induced relaxation occurred via both endothelium-dependent and -independent mechanisms. The relaxation response induced by propofol was significantly reduced by nitric oxide synthase inhibitor (l-NNA), K(+) channel blockers (tetraethylammonium and glibenclamide) in E+ and E- vessels, and by soluble guanylyl cyclase inhibitor 1H-(1,2,4) oxadiazolo (4,3-A) quinazoline-1-one and hydrogen peroxide scavenger (catalase) in E- vessels. The presence of PVAT significantly enhanced the relaxation response induced by propofol. In contrast to phenylephrine precontracted vessels in which the presence of PVAT or endothelium had an effect, in vessels precontracted with KCl, propofol-induced relaxation was similar among the 4 types of vessel preparation.
  
  
  CONCLUSIONS
  PVAT enhances the relaxation effect induced by propofol in rat aorta through both endothelium-dependent and endothelium-independent pathways thus highlighting the clinical importance of PVAT.
authors.affiliation: Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada. rmkwlee@mcmaster.ca
authors.forename: Saira I
authors.initials: SI
authors.lastname: Kassam
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.forename: Norman
authors.initials: N
authors.lastname: Buckley
authors.forename: Robert M K W
authors.initials: RM
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001013:Aorta, Thoracic / Q000473:pathology; D004727:Endothelium / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D016912:Levonorgestrel; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D016912:Levonorgestrel; D011189:Potassium Chloride; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D015742:Propofol