NitroG-L-arginine methyl ester decreases minimum alveolar concentration of isoflurane and reduces brain nitric oxide synthase activity in rats.
BACKGROUND
Nitric Oxide (NO), an endogenous messenger produced by the enzyme nitric oxide synthase (NOS), is recently introduced to be involved in inhalational anesthesia. We have previously reported that a specific NOS inhibitor, nitroG-L-arginine methyl ester (L-NAME), reduces the value of minimum alveolar concentration (MAC) for isoflurane anesthesia in rabbits. The purpose of this study is to evaluate the effects of the NOS inhibitor, L-NAME, on isoflurane MAC and NOS activity in rats.


METHODS
Adult Wistar rats receiving isoflurane inhalation were randomly divided into two groups, with eight rats in each group. In the study group, L-NAME 30 mg/kg was given 60 min before the inhalation of isoflurane. Normal saline was given to the control group instead. The data of MAC, blood pressure (BP), and heart rate (HR) were recorded. The vital signs, such as EtCO2, PaO2, and temperature, were maintained within normal ranges. The activity of NOS in cerebellum was assessed by measuring the conversion of L-[3H] arginine to L-[3H] citrulline. All data were presented as mean +/- SD. Statistical analysis was performed using Student's t-test, where P < 0.05 was considered significant.


RESULTS
In the presence of L-NAME (30 mg/kg), the MAC for isoflurane was markedly reduced from 1.6 +/- 0.20% (study group) to 1.0 +/- 0.09% (control group) (P < 0.05). The activity of cNOS in cerebellum was 220.09 +/- 23.64 (pmol/mg protein/30 min) in the control group, and in contrast a sharp reduction as low as to 115.40 +/- 24.85 (pmol/mg protein/30 min) was seen in the study group.


CONCLUSIONS
The involvement of NO in the mechanism of isoflurane anesthesia can be demonstrated by the fact that the NOS inhibitor, L-NAME reduces the level of MAC and the cerebral NOS activity in rats.
Chen
T Y
TY
Department of Anesthesiology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R.O.C.
Chang
C L
CL
Tseng
C C
CC
Tsai
Y C
YC
Cheng
J T
JT
D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007530:Isoflurane / Q000493:pharmacokinetics*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester