Microglial activation caused by a mechanism independent of TLR4 is involved in the development of morphine tolerance. Further studies are necessary to clarify the cellular mechanisms of morphine-induced microglial activation.

1 Non-adrenergic non-cholinergic (NANC) vasodilator nerves regulate tone in certain vascular beds. We have investigated the mechanisms of the NANC dilator response in the isolated small mesenteric artery of the rabbit by use of the tension myograph. 2 Small second or third order (150 ± 300 mm in diameter) arteries of the rabbit mesenteric bed were mounted in a Mulvany tension myograph. Responses to electrical ®eld stimulation (EFS) and exogenous vasodilators were investigated. 3 EFS (0.5 ± 16 Hz, 10 V, 0.3 ms for 5 s), in the presence of guanethidine (5 mM) and atropine (1 mM) produced frequency-dependent relaxation of small arteries. Pretreatment with tetrodotoxin (1 mM) abolished the relaxation and desensitization with capsaicin (10 mM) strongly inhibited the relaxation. 4 Pretreatment with a P2Y-purinoceptor antagonist, basilen blue (3 mM) or a human calcitonin generelated peptide (hCGRP) receptor antagonist, hCGRP 8 ± 37 (1 mM) suppressed the NANC relaxation by approximately 40 ± 60 % in each case and combined pretreatment almost abolished the relaxation. 5 The EFS-induced relaxation was suppressed by endothelium-removal, pretreatment with the soluble guanylyl cyclase inhibitor ODQ (1 mM) and the NO scavenger oxyhaemoglobin (OxyHb; 20 mM) but not by NO synthase inhibitors N G -nitro-L-arginine methyl ester (L-NAME; 300 mM) or N G -nitro-L-arginine (L-NOARG; 300 mM). Combined pretreatment with ODQ and CGRP 8 ± 37 almost abolished the relaxation. 6 A P2Y-purinoceptor agonist, 2-methylthio ATP, produced endothelium-dependent relaxation which was inhibited by L-NAME and ODQ (1 mM), whilst hCGRP produced endothelium-independent and ODQ-insensitive relaxation. 7 Ultraviolet light (320 nm, 5 shots over 20 s) produced relaxation that was blocked by both OxyHb and ODQ but not by N G -monomethyl-L-arginine (L-NMMA, 300 mM). 8 The present study suggests that EFS-induced NANC relaxation of the mesenteric small artery of the rabbit is mediated mainly by capsaicin-sensitive sensory C-®bres and that both ATP and CGRP are involved. The action of ATP released by EFS appears to be endothelium-dependent and involve activation of soluble guanylyl cyclase, but is resistant to inhibitors of NO synthase. The response to CGRP is endothelium-independent. These results show that ATP and CGRP account fully for the NANC relaxation of this vessel type and that the endothelium is involved in NANC-induced relaxation. The endothelium-dependent part of the response is consistent with the release of NO, either from NO synthase, incompletely inhibited by the NO synthase inhibitors, or by some preformed stores.

A study was conducted to examine the direct vascular effect of ropivacaine, in comparison with the effect of bupivacaine and lidocaine. Changes in tension induced by ropivacaine (10(-5)-3 x 10(-3) mol l-1) and lidocaine (10(-5)-10(-2) mol l-1) were examined cumulatively in vascular rings of dog femoral artery and vein under basal tension, or in those which had been precontracted with phenylephrine submaximally in Krebs' bicarbonate solution at 37 degrees C aerated with 95% O2 and 5% CO2 (pH 7.4). The change in tension induced by 10(-2) mol l-1 ropivacaine was tested under basal tension in vascular rings bathed in HEPES buffer (pH 6.8). Ropivacaine induced greater constriction than bupivacaine at concentrations over 10(-3) mol l-1 in vascular rings under basal tension (P < 0.01). The maximal contraction was induced by ropivacaine at 10(-3) mol l-1, averaging 51.5 +/- 2.8% (n = 11) and 27.0 +/- 3.7% (n = 12) of the maximal contraction induced by epinephrine in the artery and vein, respectively, and the contractions induced by ropivacaine at 10(-2) mol l-1 were 16.3 +/- 2.0% (n = 11) and 5.5 +/- 1.1% (n = 9), respectively. Phenylephrine (10(-6) mol l-1)-precontracted artery was contracted significantly by ropivacaine at 3 x 10(-4) mol l-1 and 10(-3) mol l-1, and by bupivacaine at 3 x 10(-4) mol l-1, whereas the phenylephrine (10(-6) mol l-1)-precontracted vein was relaxed by these anesthetics. Lidocaine did not exert constricting effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitroprusside (SNP) and the cGMP formation elicited by exogenous nitric oxide (NO) and SNP in rat aortas. Acetylcholine (10(-7)-10(-5) M)-induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10(-8) M)-induced relaxation was reduced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%). The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SNP (10(-7) M)-stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endothelium-dependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.

We have demonstrated that the "deep-forehead" temperature has excellent accuracy and clinically sufficient precision as well as other three core temperatures, compared with blood temperature.