Inhibition of nitric oxide synthase decreases anesthetic requirements of intravenous anesthetics in Xenopus laevis.
BACKGROUND
Acute inhibition of nitric oxide synthase (NOS) has been demonstrated to reduce the anesthetic requirements of volatile anesthetics. Recent data suggest that not only volatile but also intravenous anesthetic agents interact with nitric oxide (NO) metabolism. The aim of this study was to examine the effect of NOS inhibition by nitroG-L-arginine-methyl-ester (L-NAME) on the anesthetic action of the intravenous anesthetics thiopental, propofol, and ketamine.


METHODS
The anesthetic potencies of thiopental, propofol, and ketamine were determined in Xenopus laevis tadpoles in the absence and presence of L-NAME. Anesthesia was defined as loss of righting reflex for 5 s. A nonlinear logistic regression curve was fitted to the data and half-maximal effective concentrations (EC50) were calculated. A second set of experiments was performed with different concentrations of L-NAME in the presence of the previously determined the EC50 of the intravenous anesthetics.


RESULTS
The EC50s of the anesthetics thiopental, propofol, and ketamine were determined to be 25.5 +/- 2.0 microM, 1.9 +/- 0.1 microM, and 59.7 +/- 0.7 microM, respectively. The addition of L-NAME shifted the concentration-response curves to the left in a concentration-dependent manner. In the presence of 1 mM L-NAME, the EC50 of thiopental was reduced by 43%, the EC50 of propofol by 26%, and the EC50 of ketamine by 63%. The addition of D-NAME did not change the EC50 values of the three anesthetics. In the presence of L-arginine, the effect of L-NAME on the EC50 of thiopental was reversed. When administered by itself in a concentration range from 0.1 microM to 10 mM, L-NAME did not alter the behavior of the tadpoles.


CONCLUSIONS
The results of the present study show that acute inhibition of NOS by L-NAME results in reduced anesthetic requirements of the intravenous anesthetics thiopental, propofol, and ketamine. This interaction of acutely administered L-NAME and intravenous anesthetics indicates that the NO-cyclic guanosine 3',5'-monophosphate system is involved in mediating the anesthetic effect of these compounds.
Tonner
P H
PH
Department of Anesthesiology, University Hospital Eppendorf, Hamburg, Germany. tonner@uke.uni-hamburg.de
Scholz
J
J
Lamberz
L
L
Schlamp
N
N
Schulte am Esch
J
J
D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007649:Ketamine / Q000008:administration & dosage; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D015742:Propofol / Q000008:administration & dosage; D012018:Reflex / Q000187:drug effects; D013874:Thiopental / Q000008:administration & dosage; D014982:Xenopus laevis
D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D007649:Ketamine; D019001:Nitric Oxide Synthase; D013874:Thiopental; D019331:NG-Nitroarginine Methyl Ester; D015742:Propofol