The mechanism behind the inhibitory effect of isoflurane on angiotensin II-induced vascular contraction is different from that of sevoflurane.
BACKGROUND
Angiotensin II (Ang II)-induced vascular contraction is mediated both by a Ca(2+)-mediated signaling pathway and a Ca(2+) sensitization mechanism. We recently demonstrated that sevoflurane inhibits the contractile response to Ang II, mainly by inhibiting protein kinase C (PKC) phosphorylation that regulates myofilament Ca(2+) sensitivity, without significant alteration of intracellular Ca(2+) concentration ([Ca(2+)](i)) in rat aortic smooth muscle. The current study was designed to determine the mechanisms by which isoflurane inhibits Ang II-induced contraction of rat aortic smooth muscle.


METHODS
The effects of isoflurane on vasoconstriction, increase in [Ca(2+)](i), and phosphorylation of PKC in response to Ang II (10(-7) M) were investigated, using an isometric force transducer, a fluorometer, and Western blotting, respectively.


RESULTS
Ang II elicited a transient contraction of rat aortic smooth muscle that was associated with an increase in [Ca(2+)](i) and PKC phosphorylation. Isoflurane (1.2%-3.5%) inhibited Ang II-induced contraction of rat aortic smooth muscle in a concentration-dependent manner (P < 0.05 at 1.2%, P < 0.01 at 2.3% and 3.5% isoflurane, n = 6). Isoflurane also inhibited elevation of [Ca(2+)](i) in response to Ang II (P < 0.01 at 2.3% and 3.5% isoflurane, n = 6), but failed to affect Ang II-induced phosphorylation of PKC at concentrations up to 3.5% (n = 7).


CONCLUSIONS
These results suggest that, unlike sevoflurane, the inhibitory effect of isoflurane on Ang II-induced contraction is mainly mediated by attenuation of the Ca(2+)-mediated signaling pathway.
Ishikawa
Ai
A
Department of Anesthesiology, Wakayama Medical University, Kimiidera, Wakayama, Japan.
Ogawa
Koji
K
Tokinaga
Yasuyuki
Y
Uematsu
Nobuhiko
N
Mizumoto
Kazuhiro
K
Hatano
Yoshio
Y
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D007530:Isoflurane / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D008738:Methyl Ethers; D000804:Angiotensin II; D000077149:Sevoflurane; D007530:Isoflurane