Ketamine and midazolam differentially inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits: Role of superoxide anion and nitric oxide synthase

Atsushi Kohjitani, Takuya Miyawaki, Makoto Funahashi, Hitoshi Higuchi, Ryuji Matsuo, Masahiko Shimada

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: The authors previously reported that ketamine and midazolam inhibited nitric oxide-mediated nonadrenergic noncholinergic (NANC) lower esophageal sphincter (LES) relaxation via nitric oxide-3′,5′-cyclic guanosine monophosphate pathway modulation. The mechanisms inhibiting the NANC relaxation by ketamine and midazolam were investigated. Methods: The isometric tension of circular distal esophageal muscle strips from Japanese White rabbits was examined. NANC relaxation was induced by KCI (30 mM) in the presence of atropine (3 × 10-6 M) and guanethidine (3 × 10-6 M). Nitric oxide synthase activity in the absence and presence of ketamine and midazolam was analyzed using the biochemical conversion of L-[3H]arginine to L-[3H]citrulline. Results: The ketamine-induced inhibition of the NANC relaxation was partly reversed by superoxide dismutase (200, 400 U/ml) but not by catalase (100 U/ml). Ketamine concentration-dependently inhibited the relaxation induced by N-ethyl-ethanamine: 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (diethylamine NONOate) and S-nitrosoglutathione. The NANC relaxation itself was not affected by superoxide dismutase. The midazolam-induced inhibition of the NANC relaxation was reversed neither by superoxide dismutase nor by catalase, and midazolam did not affect the relaxations induced by nitric oxide donors. The nitric oxide synthase activity was concentration-dependently suppressed by midazolam, but there was no marked effect of ketamine. Pyrogallol, a superoxide generator, inhibited the NANC and the diethylamine NONOate-induced relaxations. The pyrogallol-induced inhibition of the NANC relaxation was reversed by superoxide dismutase. Conclusion: These findings suggest that ketamine inhibits NANC LES relaxation by the extracellular production of superoxide anion, and that midazolam inhibits it by the inhibition of nitric oxide synthase activity.

Original languageEnglish
Pages (from-to)449-458
Number of pages10
JournalAnesthesiology
Volume98
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

Fingerprint

Lower Esophageal Sphincter
Midazolam
Ketamine
Nitric Oxide Synthase
Superoxides
Rabbits
Superoxide Dismutase
Pyrogallol
Catalase
Nitric Oxide
S-Nitrosoglutathione
Guanosine Monophosphate
Guanethidine
Citrulline
Nitric Oxide Donors
Cyclic GMP
Atropine
Arginine
Muscles

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Ketamine and midazolam differentially inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits : Role of superoxide anion and nitric oxide synthase. / Kohjitani, Atsushi; Miyawaki, Takuya; Funahashi, Makoto; Higuchi, Hitoshi; Matsuo, Ryuji; Shimada, Masahiko.

In: Anesthesiology, Vol. 98, No. 2, 01.02.2003, p. 449-458.

Research output: Contribution to journalArticle

@article{f19bf34a811f418ba4d287863085e623,
title = "Ketamine and midazolam differentially inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits: Role of superoxide anion and nitric oxide synthase",
abstract = "Background: The authors previously reported that ketamine and midazolam inhibited nitric oxide-mediated nonadrenergic noncholinergic (NANC) lower esophageal sphincter (LES) relaxation via nitric oxide-3′,5′-cyclic guanosine monophosphate pathway modulation. The mechanisms inhibiting the NANC relaxation by ketamine and midazolam were investigated. Methods: The isometric tension of circular distal esophageal muscle strips from Japanese White rabbits was examined. NANC relaxation was induced by KCI (30 mM) in the presence of atropine (3 × 10-6 M) and guanethidine (3 × 10-6 M). Nitric oxide synthase activity in the absence and presence of ketamine and midazolam was analyzed using the biochemical conversion of L-[3H]arginine to L-[3H]citrulline. Results: The ketamine-induced inhibition of the NANC relaxation was partly reversed by superoxide dismutase (200, 400 U/ml) but not by catalase (100 U/ml). Ketamine concentration-dependently inhibited the relaxation induced by N-ethyl-ethanamine: 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (diethylamine NONOate) and S-nitrosoglutathione. The NANC relaxation itself was not affected by superoxide dismutase. The midazolam-induced inhibition of the NANC relaxation was reversed neither by superoxide dismutase nor by catalase, and midazolam did not affect the relaxations induced by nitric oxide donors. The nitric oxide synthase activity was concentration-dependently suppressed by midazolam, but there was no marked effect of ketamine. Pyrogallol, a superoxide generator, inhibited the NANC and the diethylamine NONOate-induced relaxations. The pyrogallol-induced inhibition of the NANC relaxation was reversed by superoxide dismutase. Conclusion: These findings suggest that ketamine inhibits NANC LES relaxation by the extracellular production of superoxide anion, and that midazolam inhibits it by the inhibition of nitric oxide synthase activity.",
author = "Atsushi Kohjitani and Takuya Miyawaki and Makoto Funahashi and Hitoshi Higuchi and Ryuji Matsuo and Masahiko Shimada",
year = "2003",
month = "2",
day = "1",
doi = "10.1097/00000542-200302000-00026",
language = "English",
volume = "98",
pages = "449--458",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Ketamine and midazolam differentially inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits

T2 - Role of superoxide anion and nitric oxide synthase

AU - Kohjitani, Atsushi

AU - Miyawaki, Takuya

AU - Funahashi, Makoto

AU - Higuchi, Hitoshi

AU - Matsuo, Ryuji

AU - Shimada, Masahiko

PY - 2003/2/1

Y1 - 2003/2/1

N2 - Background: The authors previously reported that ketamine and midazolam inhibited nitric oxide-mediated nonadrenergic noncholinergic (NANC) lower esophageal sphincter (LES) relaxation via nitric oxide-3′,5′-cyclic guanosine monophosphate pathway modulation. The mechanisms inhibiting the NANC relaxation by ketamine and midazolam were investigated. Methods: The isometric tension of circular distal esophageal muscle strips from Japanese White rabbits was examined. NANC relaxation was induced by KCI (30 mM) in the presence of atropine (3 × 10-6 M) and guanethidine (3 × 10-6 M). Nitric oxide synthase activity in the absence and presence of ketamine and midazolam was analyzed using the biochemical conversion of L-[3H]arginine to L-[3H]citrulline. Results: The ketamine-induced inhibition of the NANC relaxation was partly reversed by superoxide dismutase (200, 400 U/ml) but not by catalase (100 U/ml). Ketamine concentration-dependently inhibited the relaxation induced by N-ethyl-ethanamine: 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (diethylamine NONOate) and S-nitrosoglutathione. The NANC relaxation itself was not affected by superoxide dismutase. The midazolam-induced inhibition of the NANC relaxation was reversed neither by superoxide dismutase nor by catalase, and midazolam did not affect the relaxations induced by nitric oxide donors. The nitric oxide synthase activity was concentration-dependently suppressed by midazolam, but there was no marked effect of ketamine. Pyrogallol, a superoxide generator, inhibited the NANC and the diethylamine NONOate-induced relaxations. The pyrogallol-induced inhibition of the NANC relaxation was reversed by superoxide dismutase. Conclusion: These findings suggest that ketamine inhibits NANC LES relaxation by the extracellular production of superoxide anion, and that midazolam inhibits it by the inhibition of nitric oxide synthase activity.

AB - Background: The authors previously reported that ketamine and midazolam inhibited nitric oxide-mediated nonadrenergic noncholinergic (NANC) lower esophageal sphincter (LES) relaxation via nitric oxide-3′,5′-cyclic guanosine monophosphate pathway modulation. The mechanisms inhibiting the NANC relaxation by ketamine and midazolam were investigated. Methods: The isometric tension of circular distal esophageal muscle strips from Japanese White rabbits was examined. NANC relaxation was induced by KCI (30 mM) in the presence of atropine (3 × 10-6 M) and guanethidine (3 × 10-6 M). Nitric oxide synthase activity in the absence and presence of ketamine and midazolam was analyzed using the biochemical conversion of L-[3H]arginine to L-[3H]citrulline. Results: The ketamine-induced inhibition of the NANC relaxation was partly reversed by superoxide dismutase (200, 400 U/ml) but not by catalase (100 U/ml). Ketamine concentration-dependently inhibited the relaxation induced by N-ethyl-ethanamine: 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (diethylamine NONOate) and S-nitrosoglutathione. The NANC relaxation itself was not affected by superoxide dismutase. The midazolam-induced inhibition of the NANC relaxation was reversed neither by superoxide dismutase nor by catalase, and midazolam did not affect the relaxations induced by nitric oxide donors. The nitric oxide synthase activity was concentration-dependently suppressed by midazolam, but there was no marked effect of ketamine. Pyrogallol, a superoxide generator, inhibited the NANC and the diethylamine NONOate-induced relaxations. The pyrogallol-induced inhibition of the NANC relaxation was reversed by superoxide dismutase. Conclusion: These findings suggest that ketamine inhibits NANC LES relaxation by the extracellular production of superoxide anion, and that midazolam inhibits it by the inhibition of nitric oxide synthase activity.

UR - http://www.scopus.com/inward/record.url?scp=0037313170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037313170&partnerID=8YFLogxK

U2 - 10.1097/00000542-200302000-00026

DO - 10.1097/00000542-200302000-00026

M3 - Article

C2 - 12552205

AN - SCOPUS:0037313170

VL - 98

SP - 449

EP - 458

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 2

ER -