title: Sevoflurane does not alter norepinephrine-induced intracellular Ca²(+) changes in the diabetic rat aorta.
abstract: OBJECTIVE
  The effect of volatile anesthetics on the mechanism(s) of vascular contraction in diabetes mellitus (DM) has not been fully understood. The current study was designed to determine the effects of sevoflurane on the norepinephrine (NE)-induced changes in contractile state and intracellular Ca²(+) concentrations ([Ca²(+)](i)) in the spontaneously developing type 2 DM rat.
  
  
  METHODS
  The effects of sevoflurane on NE (10⁻⁶M)-induced vasoconstriction and increase in [Ca²(+)](i) in the aortas from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 DM model, and from age-matched control Long-Evans Tokushima Otsuka (LETO) rats were investigated using an isometric force transducer and fluorometer with fura-2 as an indicator of [Ca²(+)](i).
  
  
  RESULTS
  Norepinephrine-induced increases in tension and [Ca²(+)](i) in OLETF rats were 54.8%, 95% confidence interval (CI) 36.9-72.6% and 58.8%, 95% CI 51.5-66.1%, respectively, and in LETO rats they were 46.4%, 95% CI 39.0-53.7% and 53.8%, 95% CI 46.9-60.7%, respectively, when expressed as the percentage relative to that induced by KCl 30 mM. In LETO rats, sevoflurane at a concentration of 3.4% inhibited the vascular contraction (9.4%, 95% CI 6.3-12.6%; P < 0.001) and the increase in [Ca²(+)](i) (33.3%, 95% CI 27.4-39.2%; P = 0.002). In OLETF rats, however, sevoflurane failed to affect either the NE-induced contraction (43.6%, 95% CI 28.3-58.9%; P = 0.68) or the elevation in [Ca²(+)](i) (60.5%, 95% CI 56.3-64.8%; P = 0.93).
  
  
  CONCLUSIONS
  Sevoflurane at clinically relevant concentrations inhibited the NE-induced increase in [Ca²(+)](i) in the aortic smooth muscle from normal rats but not in that from type 2 DM rats. Thus, a Ca²(+)- signalling pathway resistant to sevoflurane appears to exist in the type 2 DM rat aorta.
authors.affiliation: Department of Anesthesiology, Japanese Red Cross Society Wakayama Medical Centre, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Fujii
authors.forename: Koji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Tokinaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iranami
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hatano
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D000077149:Sevoflurane; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D002118:Calcium; D009638:Norepinephrine