Sevoflurane does not alter norepinephrine-induced intracellular Ca²(+) changes in the diabetic rat aorta.
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.
Fujii
Keisuke
K
Department of Anesthesiology, Japanese Red Cross Society Wakayama Medical Centre, Japan.
Ogawa
Koji
K
Tokinaga
Yasuyuki
Y
Iranami
Hiroshi
H
Hatano
Yoshio
Y
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
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D002118:Calcium; D009638:Norepinephrine