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. 1995 Jul;115(6):969–974. doi: 10.1111/j.1476-5381.1995.tb15905.x

Selective inhibition by barbiturates of the synthesis of endothelium-derived hyperpolarizing factor in the rabbit carotid artery.

V Lischke 1, R Busse 1, M Hecker 1
PMCID: PMC1909012  PMID: 7582528

Abstract

1. Several lines of evidence suggest that both volatile and intravenous anaesthetics may interfere with the synthesis and release of endothelium-derived vasoactive factors. We have investigated the effects of three different barbiturates on the release of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in phenylephrine (1 microM)-preconstricted, endothelium-intact ring segments of the rabbit carotid artery. The segments were pretreated with the cyclo-oxygenase inhibitor, diclofenac (1 microM), to prevent the formation of vasoactive prostanoids, such as prostacyclin (PGI2). 2. Acetylcholine (ACh) elicited a concentration-dependent relaxation (EC50 0.15 microM) in control segments which was not significantly different from the relaxant responses of segments pretreated with methohexitone (0.03-0.3 mM), phenobarbitone (0.1-0.3 mM) or thiopentone (0.1-0.3 mM). 3. Inhibition of NO synthesis with NG-nitro-L-arginine (0.1 mM) significantly reduced the maximum relaxant response to ACh from 96 to 40%. This NO/PGI2-independent relaxation appeared to be mediated by the release of EDHF, since it was strongly diminished in the presence of the K+Ca inhibitors, tetrabutylammonium (1-3 mM) and charybdotoxin (10 nM), following preconstriction with potassium calcium (40 mM) or removal of the endothelium. Thiopentone or methohexitone markedly attenuated the EDHF-mediated relaxant response to ACh, while phenobarbitone had no effect. The endothelium-independent relaxation elicited by sodium nitroprusside (0.01-10 microM), on the other hand, was only marginally affected by these anaesthetics. 4. The cytochrome P450 inhibitor, clotrimazole (3-100 microM), mimicked the inhibitory effect of thiopentone and methohexitone on the NO/PGI2-independent relaxant response to ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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