title: Sevoflurane inhibits angiotensin II-induced Rho kinase-mediated contraction of vascular smooth muscle from spontaneously hypertensive rat.
abstract: OBJECTIVE
  Angiotensin II (Ang II)-induced vasoconstriction is mediated by changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) and myofilament Ca(2+) sensitivity. Protein kinase C- and Rho kinase-mediated signaling pathways are proposed for the regulation of the Ca(2+) sensitization mechanisms. We have demonstrated that sevoflurane inhibits Rho kinase-mediated contraction of isolated rat aortic smooth muscle. A recent study demonstrated that Rho-kinase mediated Ca(2+) sensitization was involved in the pathophysiology of hypertension. This study was designed to investigate the effects of sevoflurane on Ang II-induced Rho kinase-mediated vascular contraction in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  The effects of sevoflurane on vasoconstriction, increase in [Ca(2+)](i), and membrane translocation of Rho kinase in response to Ang II were investigated in normotensive Wistar-Kyoto rats (WKY) and SHR, using an isometric force transducer, a fluorometer, and Western blotting, respectively.
  
  
  RESULTS
  The inhibitory effects of sevoflurane on Ang II (10(-7)M)-induced contraction were greater (P < 0.05) in SHR than in WKY at the highest concentration of sevoflurane (5.1%). Y27632 (3 × 10(-7)M), a specific inhibitor of Rho kinase, inhibited the Ang II-induced contraction in SHR, but not in WKY. Sevoflurane did not affect the increases in [Ca(2+)](i) in response to Ang II in either strain. Ang II stimulated Rho kinase activity in SHR, which was almost abolished by sevoflurane at a concentration of 5.1% (P < 0.05).
  
  
  CONCLUSIONS
  These findings suggest that the inhibition of the Ang II-induced contraction by sevoflurane in SHR may be, at least in part, due to the attenuation of the Rho kinase-mediated signaling pathway.
authors.affiliation: Department of Anesthesia, Japan Red Cross Society Wakayama Medical Center, Wakayama, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Uematsu
authors.forename: Koji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Tokinaga
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tange
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hatano
mesh_terms: D000577:Amides / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D021381:Protein Transport; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077149:Sevoflurane; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D011725:Pyridines; D000804:Angiotensin II; C108830:Y 27632; D000077149:Sevoflurane; D054460:rho-Associated Kinases; D002118:Calcium