Abstract
Purpose. The present study was undertaken to examine whether interaction between halogenated volatile anesthetics and nitric oxide (NO) at soluble guanylyl cyclase (sGC) would occur in rat brain.
Methods. A soluble brain fraction was prepared from extensively perfused Sprague-Dawley rat brains by centrifugation and used as the source of sGC. sGC was incubated with NO and halogenated volatile anesthetics, and cGMP production was determined by enzyme immunoassay in aliquots of the supernatant.
Results. Halothane and sevoflurane produced significant (P<0.01) and dose-dependent inhibition of NO-stimulated sGC activity over a range of NO concentrations (2×10−9 to 2×10−5 M). Among the anesthetics, halothane tended to have a large inhibitory effect on NO-stimulated sGC activity, which was, however, not significant. sGC activity was also inhibited by both anesthetics (P<0.05) in the absence of NO stimulation. GTP dose-dependently increased both NO-stimulated and-nonstimulated sGC activities. Halothane and sevoflurane decreased these activities (P<0.01), but the inhibition by these anesthetics was not significant at higher GTP concentrations.
Conclusion. These results suggest that halogenated volatile anesthetics can attenuate the activity of NO-stimulated sGC by competing with NO for the NO binding site on the enzyme.
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References
Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide froml-arginine. Nature (Lond) 333:664–666
Azuma H, Ishikawa M, Sekizawa S (1986) Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 88:411–415
Bredt DS, Snyder SH (1992) Nitric oxide, a novel neuronal messenger. Neuron 8:3–11
Olstein EH, Wood KS, Ignarro LJ (1982) Purification and properties of heme-deficient soluble guanylate cyclase: effects of heme and other factors on enzyme activation of NO, NO-heme and protoporphyrin. Arch Biochem Biophys 218:187–198
Vincent SR, Hope BT (1992) Neurons that say NO. Trends Neurosci 15:108–117
Garthweite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMDA receptor suggests role as intracellular messenger in the brain. Nature (Lond) 336:385–388
Garthweite J, Garthweite G, Palmer RMJ, Moncada S (1989) NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. Eur J Pharmacol 172:413–416
Bredt DS, Snyder SH (1989) Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci USA 86:9030–9033
Kant GJ, Muller TW, Lenox RH, Meyerhoff JL (1980) In vivo effects of pentobarbital and halothane anesthesia on levels of adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in rat brain regions and pituitary. Biochem Pharmacol 29:1891–1896
Vulliemoz Y, Verosky M, Alpert M, Triner L (1983) Effects of enflurane on cerebellar cGMP and on motor activity in the mouse. Br J Anesth 55:79–84
Gonzales JM, Loeb AL, Reichard PS, Irvine S (1995) Ketamine inhibits glutamateN-methyl-d-aspartate and quisqualate-stimulated cGMP production in cultured cerebral neurons. Anesthesiology 82:205–213
Johns RA, Moscicki JC, DiFazio CA (1992) Nitric oxide synthase inhibitor dose-dependently and reversibly reduces the threshold for halothane anesthesia. Anesthesiology 77:779–784
Ichinose F, Huang PL, Zapol WM (1995) Effects of targeted neuronal nitric oxide synthase gene disruption and nitroG-l-arginine methylester on the threshold for isoflurane anesthesia. Anesthesiology 83:101–108
Pajewski TN, DiFazio CA, Moscicki JC, Johns RA (1996) Nitric oxide synthase inhibitors 7-nitro indazole and nitroG-l-arginine methyl ester, dose dependently reduced the threshold for isoflurane anesthesia. Anesthesiology 85:1111–1119
Kawabata A, Umeda N, Takagi H (1993)l-Arginine exerts a dual role in niciceptive processing in the brain: involvement of the kyotorphin-Met-enkephalin pathway and NO-cyclic GMP pathway. Br J Pharmacol 109:73–79
Ahr HJ, King LJ, Nastainczyk W, Ullrich V (1982) The mechanism of reductive dehalogenation of halothane by liver cytochrome P-450. Biochem Pharmacol 41:383–390
Baker MT, Nelson RM, Van Dyke RA (1983) The release of inorganic fluoride form halothane and halothane metabolites by cytochrome P-450, hemin and hemoglobin. Drug Metab Dispos 11:308–311
Masaki E, Van Dyke RA (1992) Effect of nitric oxide on the anaerobic metabolism of halothane by rat hepatic cytochrome P-450. FASEB J 6:A1568 (abstract)
Hart JL, Jing M, Bina S, Freas W, Van Dyke RA, Muldoon SM (1993) Effects of halothane on EDRF/cGMP-mediated vascular smooth muscle relaxation. Anesthesiology 79:323–331
Jing M, Hart JL, Masaki E, Van Dyke RA, Bina S, Muldoon SM (1995) Vascular effects of halothane and isoflurane: cGMP dependent and independent actions. Life Sci 56:19–29
Zuo Z, Johns RA (1995) Halothane, Enflurane, and isoflurane do not affect the basal or agonist-stimulated activity of partially isolated soluble and particulate guanylyl cyclases of rat brain. Anesthesiology 83:395–404
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein binding. Anal Biochem 72:248–254
Moy JA, Bates JN, Fisher RA (1991) Effects of nitric oxide on platelet-activation factor and α-adrenergic-stimulated vasoconstriction and glycogenolysis in perfused rat liver. J Biol Chem 266:8092–8096
Myers PR, Minor RJ Jr, Bates JN, Harrison DG (1990) Vasorelaxant properties of the endothelium-derived relaxing factor more closely resembles-nitrosocysteine than nitric oxide. Nature (Lond) 345:161–163
Ignarro LJ, Wood KS, Wolin MS (1982) Activation of purified soluble guanylate cyclase by protoporphyrin IX. Proc Natl Acad Sci USA 79:2870–2873
Brume B, Ullrich V (1987) Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol 32:497–504
Marks GS, Brien JF, Nakatsu K, McLaughlin BE (1991) Does carbon monoxide have a physiological function? Trends Pharmacol Sci 12:185–188
Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (London) 327:524–526
Ignarro LJ, Adams JB, Horwitz PM, Wood KS (1986) Activation of soluble guanylate cyclase by NO-hemeproteins involves NO-heme change. Comparison of heme-containing and heme-deficient enzyme forms. J Biol Chem 261:4997–5002
Baker MT, Van Dyke RA (1992) Biochemical and toxicological aspects of the volatile anesthetics. In: Barash PG, Cullen BF, Stoelting RK (eds) Clinical anesthesia, 2nd edn JB Lippincott, Philadelphia, pp 467–480
Van Dyke RA, Wineman CG (1971) Enzymatic dechlorination: dechlorination of chloroethanes and propanes in vitro. Biochem Pharmacol 20:463–470
Jing M, Bina S, Verma A, Hart JL, Muldoon SM (1996) Effects of halothane and isoflurane on carbon monoxide-induced relaxations in the rat aorta. Anesthesiology 85:347–354
Blaise G, To Q, Parent M, Lagarde B, Asenjo F, Sauve R (1994) Does halothane interfere with the release action or stability of endothelium-derived relaxing factor/nitric oxide? Anesthesiology 80:417–426
Yoshida K, Okabe E (1992) Selective impairment of endothelium-dependent relaxation by sevoflurane: oxygen free radicals participation. Anesthesiology 76:440–447
Terasako K, Nakamura K, Miyawaki I, Toda H, Karuyama M, Mori K (1994) Inhibitory effects of anesthetics on cyclic guanosine monophosphate (cGMP) accumulation in rat cerebellar slices. Anesth Analg 79:91–96
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Masaki, E., Kondo, I. Attenuation of nitric oxide-stimulated soluble guanylyl cyclase from the rat brain by halogenated volatile anesthetics. J Anesth 12, 81–86 (1998). https://doi.org/10.1007/BF02480777
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DOI: https://doi.org/10.1007/BF02480777