title: Sevoflurane and isoflurane inhibit KCl-induced Class II phosphoinositide 3-kinase α subunit mediated vasoconstriction in rat aorta.
abstract: Class II phosphoinositide 3-kinase α-isoform (PI3K-C2α) is involved in regulating KCl-induced vascular smooth muscle contraction. The current study was to investigate the effects of sevoflurane (SEVO) and isoflurane (ISO) on KCl-elicited PI3KC2α mediated vasoconstriction in rat aortic smooth muscle.
  
  
  
  Isometric force, in the absence or presence of SEVO or ISO (1 ~ 3 minimum alveolar concentration, MAC), PI3K inhibitor LY294002, Rho kinase inhibitor Y27632, and membrane translocation of PI3K-p85, PI3K-C2α, Rho kinase (Rock II), or phosphorylation of MYPT1/Thr853, MYPT1/Thr696, CPI-17/Thr38 and MLC in response to KCl (60 mM) was measured by using isometric force transducer and western blotting analysis, respectively.
  
  
  
  KCl elicited a rapid and sustained contraction of rat aortic smooth muscle that was inhibited by both SEVO and ISO in a concentration-dependent manner, and also suppressed by LY294002 (1 mM) and Y27632 (1 uM). LY294002 (1 mM) and Y27632 (1 uM) also inhibited KCl-induced MLC phosphorylation. LY294002 (1 mM) inhibited KCl-induced PI3K-p85, PI3K-C2α membrane translocation in response to KCl (p <0.05, p < 0.01, respectively). Not only Y27632 (1 uM), but also LY294002 (1 mM), inhibited KCl-induced Rock-II membrane translocation (p < 0.01). SEVO and ISO inhibited KCl-stimulated MLC phosphorylation, PI3K-C2α and Rock-II,not PI3K p85 membrane translocation in a concentration-dependent manner in rat aorta. Both SEVO and ISO suppressed the MYPT1/Thr853, not MYPT1/Thr696 and CPI-17/Thr38, MLC phosphorylation in response to KCl.
  
  
  
  PI3K-C2α mediates part of SEVO and ISO-mediated vasodilation in rat aorta. The cellular mechanisms underlying the inhibitory effect of volatile anesthetics might be mediated by KCl/PI3K-C2α/Rho kinase/MYPT1/MLC pathway.
authors.affiliation: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Shaozhong
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, 250012, China. qifeng66321@sina.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Qi
mesh_terms: D000577:Amides / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002867:Chromones / Q000494:pharmacology; D058541:Class II Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000577:Amides; D018685:Anesthetics, Inhalation; D002867:Chromones; D008738:Methyl Ethers; D009025:Morpholines; D018994:Myosin Light Chains; D011725:Pyridines; C108830:Y 27632; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000077149:Sevoflurane; D011189:Potassium Chloride; D007530:Isoflurane; D058541:Class II Phosphatidylinositol 3-Kinases; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1
keywords: Isoflurane; KCl; Myosin light chain phosphatase; Phosphoinositide 3 kinase; Rho kinase; Sevoflurane