Intravenous anesthetics inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation via nitric oxide-cyclic guanosine monophosphate pathway modulation in rabbits

Atsushi Kohjitani, Takuya Miyawaki, Makoto Funahashi, Yoshihiro Mitoh, Ryuji Matsuo, Masahiko Shimada

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Nonadrenergic noncholinergic (NANC) nerves have important roles in the regulation of the lower esophageal sphincter (LES) motility and function. The effects of thiopental, ketamine, and midazolam on NANC LES relaxation were investigated. Methods: The isometric tension of circular muscle strips from Japanese White rabbits was examined. The NANC relaxation was induced by KCI (30 mM) in the presence of atropine (3 × 10 -6 M) and guanethidine (3 × 10 -6 M). The modifications of the NANC and sodium nitroprusside (SNP; 10 -5 M)-induced relaxation by the anesthetics were examined. The content of 3′,5′-cyclic guanosine monophosphate (CGMP) was measured by radioimmunoassay. Results: The KCl-induced relaxation was abolished by pretreating with tetrodotoxin (10 -6 M). The NANC relaxation was inhibited in the presence of N G-nitro-L-arginine (L-NNA; 3 × 10 -5 M), methylene blue (10 -6 M), apamin (10 -7 M), and glibenclamide (10 -5 M). The SNP-induced relaxation was inhibited by methylene blue but was not affected by tetrodotoxin, L-NNA, apamin, or glibenclamide. Ketamine (EC 50 = 8.8 × 10 -5 M) and midazolam (EC 50 = 4.8 × 10-6 M) suppressed the NANC response in a concentration-dependent manner, leaving SNP-induced response unchanged. Thiopental altered neither of the relaxations. cGMP content was decreased in the presence of ketamine and midazolam. Conclusion: The NANC relaxation was mediated by nitric oxide and by low-conductance calcium- and adenosine triphosphate-sensitive potassium channels of smooth muscle. The modulation of the nitric oxide-CGMP pathway was related, at least in part, to the inhibitory actions of ketamine and midazolam on the NANC LES relaxation.

Original languageEnglish
Pages (from-to)176-183
Number of pages8
JournalAnesthesiology
Volume95
Issue number1
Publication statusPublished - 2001
Externally publishedYes

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Intravenous Anesthetics
Lower Esophageal Sphincter
Midazolam
Cyclic GMP
Ketamine
Nitric Oxide
Rabbits
Guanosine Monophosphate
Apamin
Single Nucleotide Polymorphism
Thiopental
Glyburide
Methylene Blue
Tetrodotoxin
Guanethidine
Muscle Tonus
Potassium Channels
Nitroprusside
Atropine
Radioimmunoassay

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Intravenous anesthetics inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation via nitric oxide-cyclic guanosine monophosphate pathway modulation in rabbits. / Kohjitani, Atsushi; Miyawaki, Takuya; Funahashi, Makoto; Mitoh, Yoshihiro; Matsuo, Ryuji; Shimada, Masahiko.

In: Anesthesiology, Vol. 95, No. 1, 2001, p. 176-183.

Research output: Contribution to journalArticle

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abstract = "Background: Nonadrenergic noncholinergic (NANC) nerves have important roles in the regulation of the lower esophageal sphincter (LES) motility and function. The effects of thiopental, ketamine, and midazolam on NANC LES relaxation were investigated. Methods: The isometric tension of circular muscle strips from Japanese White rabbits was examined. The NANC relaxation was induced by KCI (30 mM) in the presence of atropine (3 × 10 -6 M) and guanethidine (3 × 10 -6 M). The modifications of the NANC and sodium nitroprusside (SNP; 10 -5 M)-induced relaxation by the anesthetics were examined. The content of 3′,5′-cyclic guanosine monophosphate (CGMP) was measured by radioimmunoassay. Results: The KCl-induced relaxation was abolished by pretreating with tetrodotoxin (10 -6 M). The NANC relaxation was inhibited in the presence of N G-nitro-L-arginine (L-NNA; 3 × 10 -5 M), methylene blue (10 -6 M), apamin (10 -7 M), and glibenclamide (10 -5 M). The SNP-induced relaxation was inhibited by methylene blue but was not affected by tetrodotoxin, L-NNA, apamin, or glibenclamide. Ketamine (EC 50 = 8.8 × 10 -5 M) and midazolam (EC 50 = 4.8 × 10-6 M) suppressed the NANC response in a concentration-dependent manner, leaving SNP-induced response unchanged. Thiopental altered neither of the relaxations. cGMP content was decreased in the presence of ketamine and midazolam. Conclusion: The NANC relaxation was mediated by nitric oxide and by low-conductance calcium- and adenosine triphosphate-sensitive potassium channels of smooth muscle. The modulation of the nitric oxide-CGMP pathway was related, at least in part, to the inhibitory actions of ketamine and midazolam on the NANC LES relaxation.",
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AU - Kohjitani, Atsushi

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AU - Funahashi, Makoto

AU - Mitoh, Yoshihiro

AU - Matsuo, Ryuji

AU - Shimada, Masahiko

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