Nitro^G-L-arginine Methyl Ester Decreases Minimum Alveolar Concentration of Isoflurane and Reduces Brain Nitric Oxide Synthase Activity in Rats

Nitro^G-L-arginine Methyl Ester可降低Isoflurane最小肺泡內濃度（MAC）及腦內一氧化氮形成酶的活性

陳宗鷹(Tsung-Ying Chen) ； 張傳林(Chuan-Lin Chang) ； 曾稼志(Chia-Chih Tseng) ； 蔡玉娟(Yu-Chuan Tsai) ； 鄭瑞棠(Juei-Tang Cheng)

《Acta Anaesthesiologica Sinica》 36卷3期 (1998/09) Pp. 127-131

摘要

Background: Nitric Oxide (NO), an endogenous messenger produced by the enzyme nitric oxide (NOS), is recently introduced to be involved in inhalational anesthesia. We have previously reported that a specific NOS inhibitor, nitro^G-L-arginine methyl ester (L-NAME), reduces the value of minimum alveolar concentration (MAC) for isoflurane anesthesia in rabbits. The purpose of this study is to evaluate the effects of the NOS inhibitor, L-NAME, on isoflurane MAC and NOS activity in rats. Methods: Adult Wistar rats receiving isoflurane inhalation were randomly divided into two groups, with eight rats in each group. In the study group, L-NAME 30 mg/kg was given 60 min before the inhalation of isofnlurane. Normal saline was given to the control group instead. The data of MAC, blood pressure (BP), and heart rate (HR) were recorded. The vital signs, such as EtCO_2, PaO_2, and temperature, were maintained within normal ranges. The activity of NOS in cerebellum was assessed by measuring the conversion of L-[^3H] arginine to L-[^3H] citrulline. All data were presented as mean ± SD. Statistical analysis was performed using Student's t-test, where P＜0.05 was considered significant. Results: In the presence of L-NAME (30mg/kg), the MAC for isoflurane was markedly reduced from 1.6 ± 0.20% (study group) to 1.0±0.09% (control group) (P＜0.05).The activity of cNOS in cerebellum was 220.09±23.64 (pmol/mg protein /30 min)in the control group, and in contrast a sharp reduction as low as to 115.40 24.85 (pmol/mg protein/30 min) was seen in the study group. Conclusions: The involvement of NO in the mechanism of isoflurane anesthesia can be demonstrated by the fact that the NOS inhibitor, L-NAME reduces the level of MAC and the cerebral NOS activity in rats.

關鍵字

Anesthetics, inhalation: isoflurane ； Neurotransmitter: nitric oxide ； Nitric oxide synthase inhibitor: nitro^G-L-arginine methyl ester (L-NAME) ； Animal: rat

並列摘要

背景：一氧化氮（NO）已被証實在中樞神經系統內擔任著一種神經傳遞控制的角色，且與吸入性麻醉劑作用機轉有關。我們先前研究顯示使用抑制一氧化氮形成酶的藥物（L-NAME）於兔子身上對isoflurane最小肺泡內濃度（MAC）有降低現象。本研究則使用大白鼠，希望進一步探討一氧化氮形成酶抑制劑對isoflurane MAC與腦中一氧化氮形成酶（NOS）活性的影響。方法：選用16隻大白鼠，每組8隻。研究組於實驗前60分鐘靜脈注射一次L-NAME（30kg／mg）；對照組則給與同量生理食鹽水。測定兩組的MAC、血壓以及心跳並分別記錄之，其他的資料如EtCO_2，血中含氧量及溫度則都保持在正常範圍。腦部NOS之活性係由L-[^3H]arginine變為L-[^3H]citrulline來測定。所有資料以中間值加減標準誤差來表示。統計學上則以Student's t-test來計算，當P＜0.05時視為有意義的。結果：對照組的isoflurane在肺泡內最小的需要濃度（MAC）為1.60 ± 0.20%，而在注射L-NAME的研究組之isoflurane的MAC則為1.00 ± 0.09％（P＜0.05）。至於腦部cNOS之活性對照組為220.09 ± 23.64（pmol／mg protein／30min），而研究組則為115.40 ± 24.85（pmol／mg protein／30min）。結論：注射L-NAME的研究組之isoflurane的MAC比對照組的isoflurane之MAC為低，同時腦部cNOS活性亦降低，由此可証明一氧化氮（NO）確實參與isoflurane的麻醉機轉。

並列關鍵字

吸入性麻醉劑：isoflurane ； 神經傳導物質：一氧化氮 ； 一氧化氮形成酶抑制劑：L-NAME ； 動物：大白鼠