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GENERAL ARTICLES

Halothane Minimum Alveolar Anesthetic Concentration and Neuronal Nitric Oxide Synthase Activity of the Dorsal Horn and the Locus Ceruleus in Rats

Taeko Fukuda, MD, PhD^*, Shigeyuki Saito, MD, PhD^*, Shigehito Sato, MD, PhD, Izumi Harukuni, MD^*, and Hidenori Toyooka, MD, PhD^*

*Department of Anesthesiology, Institute of Clinical Medicine, Tsukuba University, Tsukuba-city, Ibaraki; and Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu-city, Sizuoka, Japan

Address correspondence and reprint requests to Taeko Fukuda, MD, PhD, Department of Anesthesiology, Institute of Clinical Medicine, Tsukuba University, Tsukuba-city, Ibaraki, 305-8575, Japan. Address e-mail to taekof{at}md.tsukuba.ac.jp

There is some evidence of a relationship between nitric oxide and pain control pathways. However, it is still controversial whether nitric oxide synthase (NOS) inhibitors affect minimum alveolar anesthetic concentration (MAC). We examined the effects of 7-nitro indazole (7-NI), a selective neuronal NOS (nNOS) inhibitor, on halothane MAC. With nicotinamide adenine dinucleotide phosphate diaphorase histochemistry, we also investigated the nNOS activity of the dorsal horn and the locus ceruleus in 26 Sprague-Dawley rats. 7-NI (100, 500, 1000 mg/kg intraperitoneally) reduced halothane MAC to 0.34% ± 0.12%, 0.1% ± 0.03%, and 0.05% ± 0.12%, dose dependently (P < 0.01). 7-NI also reduced the number of nicotinamide adenine dinucleotide phosphate diaphorase-positive cells by 20% to 65% (P < 0.05 or 0.01) and the staining intensity of the axons in the locus ceruleus and lumbar and thoracic spinal cord as compared with the control group. 7-NI reduced the MAC observed with halothane anesthesia, which was accompanied by nNOS activity suppression in the spinal cord and the locus ceruleus. Our results support the hypothesis that the nitric oxide signaling pathway is related to MAC.

Implications: We examined the effects of a selective neuronal nitric oxide synthase inhibitor, 7-nitro indazole, on halothane minimum alveolar anesthetic concentration and measured the nitric oxide synthase activity in the spinal cord and the locus ceruleus of Sprague-Dawley rats using nicotinamide adenine dinucleotide phosphate diaphorase staining method. 7-Nitro indazole decreased both the minimum alveolar anesthetic concentration and neuronal nitric oxide synthase activity.

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