Halothane but not isoflurane attenuates interleukin 1beta-induced nitric oxide synthase in vascular smooth muscle.
BACKGROUND
Inducible nitric oxide synthase (iNOS) is induced by endotoxin or cytokines, such as interleukin (IL)-1, through a protein synthesis pathway. Halothane reportedly inhibits protein synthesis in various tissues. The aim of the current study was to examine the effect of halothane on the IL-1beta-evoked induction of NOS in vascular smooth muscle.


METHODS
After removal of the endothelium, arterial rings of rat aorta were mounted in an isometric force recording system. The effects of halothane (1.0-3.0%) or isoflurane (3.0%) on IL-1beta (20 ng/ml)-induced inhibition of the contractile responses to KCl (30 mM) and phenylephrine (10(-9)-10(-5) M) were studied. The cyclic guanosine monophosphate and cyclic adenosine monophosphate contents were determined by radioimmunoassay. Expression of iNOS and iNOS mRNA were measured by Western or Northern blot analysis, respectively.


RESULTS
Halothane (1.0-3.0%) but not isoflurane (3%) significantly reduced the ML-1beta-induced inhibition of contraction in a concentration-dependent manner. The cyclic guanosine monophosphate content of the vascular smooth muscle increased significantly after a 5-h exposure to IL-1beta. Halothane at 3.0% significantly inhibited the increase in cyclic guanosine monophosphate content induced by IL-1beta. Halothane had no effect on cyclic adenosine monophosphate content. IL-1beta-induced expression of iNOS and iNOS mRNA in the rat aorta were inhibited significantly by halothane.


CONCLUSIONS
The current study demonstrated that halothane but not isoflurane inhibits IL-1beta-stimulated hyporesponsiveness to vasoconstrictive agents in vascular smooth muscle and that this inhibitory effect of halothane involves the inhibition of iNOS mRNA expression. Thus, these findings suggest that halothane may have some sites to affect nitric oxide-signaling pathway.
Maeda
H
H
Department of Anesthesia, Wakayama Medical College, Japan.
Iranami
H
H
Yamamoto
M
M
Ogawa
K
K
Morikawa
Y
Y
Senba
E
E
Hatano
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D012333:RNA, Messenger; D007530:Isoflurane; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000262:Adenylyl Cyclases; D006221:Halothane