Volatile anesthetics inhibit angiotensin II-induced vascular contraction by modulating myosin light chain phosphatase inhibiting protein, CPI-17 and regulatory subunit, MYPT1 phosphorylation.
BACKGROUND
Vascular contraction is regulated by myosin light chain (MLC) phosphorylation. Inhibition of MLC phosphatase (MLCP) increases MLC phosphorylation for a given Ca(2+) concentration, and results in promoting myofilament Ca(2+) sensitivity. MLCP activity is mainly determined by protein kinase C (PKC) and Rho kinase through the phosphorylation of both PKC-potentiated inhibitory protein (CPI-17) and myosin phosphatase target subunit (MYPT1). We have previously demonstrated that sevoflurane inhibits PKC phosphorylation and membrane translocation of Rho kinase. This study was designed to investigate the effects of sevoflurane and isoflurane on CPI-17, MYPT1, and MLC phosphorylation in response to angiotensin II (Ang II) in rat aortic smooth muscle.


METHODS
The effects of sevoflurane or isoflurane (1-3 minimum alveolar concentration) on the vasoconstriction and phosphorylation of MLC, CPI-17, MYPT1 at Thr853 and MYPT1 at Thr696 in response to Ang II were investigated using isometric force transducer and Western blotting, respectively.


RESULTS
Ang II (10(-7) M) elicited a transient contraction of rat aortic smooth muscle that was inhibited by both sevoflurane and isoflurane in a concentration-dependent manner. Ang II also induced an increase in the phosphorylation of MLC, CPI-17, MYPT1/Thr853 and MYPT1/Thr696. Sevoflurane inhibited the phosphorylation of MLC, CPI-17, and MYPT1/Thr853 in response to Ang II in a concentration-dependent manner. Isoflurane also inhibited MLC phosphorylation in response to Ang II, which was associated with decreases in MYPT1/Thr853, but not in CPI-17. Neither sevoflurane nor isoflurane affected the Ang II-induced phosphorylation of MYPT1/Thr696.


CONCLUSIONS
Although both volatile anesthetics inhibited Ang II-induced vasoconstriction and MLC phosphorylation to similar extent, the mechanisms behind the inhibitory effects of each anesthetic on MLCP activity appear to differ.
Qi
Feng
F
Department of Anesthesiology, Wakayama Medical University, Wakayama City 641-0012, Japan.
Ogawa
Koji
K
Tokinaga
Yasuyuki
Y
Uematsu
Nobuhiko
N
Minonishi
Toshiyuki
T
Hatano
Yoshio
Y
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D018994:Myosin Light Chains / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1 / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D000077149:Sevoflurane; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors*
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D009124:Muscle Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; C491519:Ppp1r14a protein, rat; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D000077149:Sevoflurane; D007530:Isoflurane; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1