title: The inhibitory effects of sevoflurane on angiotensin II- induced, p44/42 mitogen-activated protein kinase-mediated contraction of rat aortic smooth muscle.
abstract: Sevoflurane dilates blood vessels and reduces arterial blood pressure in a dose-dependent manner. Angiotensin II (Ang II) is one of the primary regulators of vascular tension and arterial blood pressure, and the p44/42 mitogen-activated protein kinases (p44/42 MAPK) are involved in Ang II-mediated vascular smooth muscle contraction. We designed this study to examine the effects of sevoflurane on Ang II-induced, p44/42 MAPK-mediated contraction of rat aortic smooth muscle. The effects of the p44/42 MAPK kinase (MEK1/2) inhibitor, PD 098059 (10(-5) molar [M], 5 x 10(-5) M and 10(-4) M), and sevoflurane (1.7%, 3.4%, and 5.1%) on Ang II-induced contraction and p44/42 MAPK phosphorylation were tested in rat aortic smooth muscle, using isometric force measurement and Western blot analysis, respectively. Ang II induced both a transient contractile response and phosphorylation of p44/42 MAPK, which were significantly attenuated by PD 098059 (P < 0.05-0.01). Sevoflurane inhibited Ang II-induced contractile response in a dose-dependent manner (P < 0.05 and 0.01 in response to 3.4% and 5.1% sevoflurane, respectively). Sevoflurane also dose-dependently depressed Ang II-elicited p44/42 MAPK phosphorylation (P < 0.01 in response to 3.4% and 5.1% sevoflurane). These results suggest that the inhibitory effect of sevoflurane on Ang II-induced vasoconstriction is, at least in part, caused by the inhibition of the p44/42 MAPK-mediated signaling pathway.
  
  
  CONCLUSIONS
  The present study demonstrates that sevoflurane can dose-dependently inhibit both angiotensin II (Ang II)-induced contraction and p44/42 MAPK phosphorylation of rat aortic smooth muscle. These data suggest that sevoflurane-produced inhibition of Ang II-induced vasoconstriction is, at least in part, caused by depression of the p44/42 MAPK-mediated signaling pathway.
authors.affiliation: *Department of Anesthesiology and †Surgical Operating Center, Wakayama Medical University, Wakayama City, Japan.
authors.forename: Jingui
authors.initials: J
authors.lastname: Yu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Tokinaga
authors.forename: Koji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hatano
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010766:Phosphorylation; D051381:Rats; D000077149:Sevoflurane; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D005419:Flavonoids; D008738:Methyl Ethers; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000077149:Sevoflurane; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one