title: Propofol induces excessive vasodilation of aortic rings by inhibiting protein kinase Cβ2 and θ in spontaneously hypertensive rats.
abstract: Exaggerated hypotension following administration of propofol is strongly predicted in patients with hypertension. Increased PKCs play a crucial role in regulating vascular tone. We studied whether propofol induces vasodilation by inhibiting increased PKC activity in spontaneously hypertensive rats (SHRs) and, if so, whether contractile Ca2+sensitization pathways and filamentous-globular (F/G) actin dynamics were involved.
  
  
  
  Rings of thoracic aorta, denuded of endothelium, from normotensive Wistar-Kyoto (WKY) rats and SHR were prepared for functional studies. Expression and activity of PKCs in vascular smooth muscle (VSM) cells were determined by Western blot analysis and elisa respectively. Phosphorylation of the key proteins in PKC Ca2+sensitization pathways was also examined. Actin polymerization was evaluated by differential centrifugation to probe G- and F-actin content.
  
  
  
  Basal expression and activity of PKCβ2 and PKCθ were increased in aortic VSMs of SHR, compared with those from WKY rats. Vasorelaxation of SHR aortas by propofol was markedly attenuated by LY333531 (a specific PKCβ inhibitor) or the PKCθ pseudo-substrate inhibitor. Furthermore, noradrenaline-enhanced phosphorylation, and the translocation of PKCβ2 and PKCθ, was inhibited by propofol, with decreased actin polymerization and PKCβ2-mediated Ca2+sensitization pathway in SHR aortas.
  
  
  
  Propofol suppressed increased PKCβ2 and PKCθ activity, which was partly responsible for exaggerated vasodilation in SHR. This suppression results in inhibition of actin polymerization, as well as that of the PKCβ2- but not PKCθ-mediated, Ca2+sensitization pathway. These data provide a novel explanation for the unwanted side effects of propofol.
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Huixuan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Aizhong
authors.initials: A
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D058105:Polymerization / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000199:Actins; D047428:Protein Kinase Inhibitors; C081975:protein kinase C eta; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D015742:Propofol