Sevoflurane, but not propofol, prevents Rho kinase-dependent contraction induced by sphingosylphosphorylcholine in the porcine coronary artery.
BACKGROUND
Sphingosylphosphorylcholine may induce coronary vasospasm by the activation of Rho kinase. We designed the current study to examine the differential effects of anesthetics on Rho kinase activation induced by sphingosylphosphorylcholine in porcine coronary arteries.


METHODS
Rings of porcine coronary artery without endothelium were prepared in tissue bath containing modified Krebs-Ringer bicarbonate solution. Using isometric force recording, concentration-response curves in response to sphingosylphosphorylcholine were obtained in the absence or in the presence of sevoflurane, propofol, or a selective Rho kinase inhibitor Y27632, which was added 15 min before the application of sphingosylphosphorylcholine. Intracellular translocation of Rho A toward the plasma membrane and phosphorylation of the myosin-targeting subunit of myosin light chain phosphatase were also evaluated by Western blotting.


RESULTS
Sphingosylphosphorylcholine (10(-7) to 10(-5) M) produced contraction of the porcine coronary artery, which was abolished by a selective Rho kinase inhibitor Y27632 (2 x 10(-6) M). Sevoflurane (1.7%) reduced sphingosylphosphorylcholine-induced coronary artery constriction, and the higher concentration (3.4%) abolished it (P < 0.05). In contrast, propofol (3 x 10(-6) M and 10(-5) M) had no effect on coronary artery constriction due to sphingosylphosphorylcholine. Sevoflurane, but not propofol, reduced intracellular translocation of Rho A toward the plasma membrane. Sevoflurane and Y27632, but not propofol, similarly decreased (64.4% or 70.8% reduction, respectively, P < 0.05) phosphorylation of the myosin-targeting subunit of myosin light chain phosphatase.


CONCLUSIONS
Sphingosylphosphorylcholine induces coronary vasocontriction via activation of Rho kinase. Sevoflurane, but not propofol, inhibits this pathway, resulting in prevention of vasoconstriction.
Kinoshita
Hiroyuki
H
Department of Anesthesiology, Wakayama Medical University, Kimiidera, Wakayama, Wakayama, Japan. hkinoshi@pd5.so-net.ne.jp
Matsuda
Naoyuki
N
Kimoto
Yoshiki
Y
Tohyama
Setsuko
S
Hama
Keiko
K
Nakahata
Katsutoshi
K
Hatano
Yoshio
Y
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008738:Methyl Ethers / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077149:Sevoflurane; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D008738:Methyl Ethers; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D000077149:Sevoflurane; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D013110:Sphingosine; D015742:Propofol