抑制脊髓一氧化氮和肝臟微循酶對血壓變異性 環之作用

Blockade of Spinal Nitric Oxide Synthase on Blood Pressure Variability and Hepatic Microcirculation

背景：本實驗室過去發現，椎管內注射一氧化氮酶阻斷劑A^-nitro-L-arginine methyl ester （L- NAME）會引起血壓增高，而且隨使用劑量成正比。本研究目的是使用血壓訊號頻譜分析來探 討自主神經參與其中的角色，同時探討椎管內注射一氧化氮酶阻斷劑對肝臟微循環的作用。方法：本實驗使用八隻Spraque-Dawley大鼠，以ketamine 120 mg/lcg腹腔注射誘導及30 mg/lcg/h靜脈滴注維持麻醉。手術準備包括右股動脈及靜脈導管植入，分別用作記錄血壓訊號和給藥， 我們在大鼠身上進行迷你開腹手術，同時在肝臟中葉植入微透析管及置放雷射杜卜勒探針測 量其微循環參數，實驗時，於椎管內間隔兩小時注射L-NAME，劑量分別是0、0.37、0.74、和1.48 fimol 。結果：隨注射之劑量增加血壓呈正向增高。同時，代表血管運動張力的血壓頻譜極低頻其強 度也隨劑量增高，而代表自主神經平衡的低頻與高頻比值則遞減，表示此時感壓反射起動而 副交感神經較強，微透析測得代表肝臟代謝功能的monoethylglycinexylidide （MEGX）此時並未改 變，杜卜勒血流量在低劑量0.37 jjmol時稍減少，但一般均呈穩定狀態。結論：在本實驗中，我們認為阻斷脊髓內一氧化氮酶活性會增高血管運動張力，進而增高動 脈血壓，感壓反射不受脊髓內一氧化氮酶活性抑制所影響仍可起動，交感神經抑制，副交感 神經相對強勢。此時的肝臟微循環則不太受到影響而相當穩定。

Background: We previously demonstrated that intrathecal administration of iV^-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased systemic arterial blood pressure in a dose-dependent man-ner in rats. The aim of the study was to investigate the participation of autonomic nervous system on L-NAME- induced hypertension and also illuminate its effects on hepatic microcirculation in rats. Methods: Eight Spraque-Dawley rats were used and initially anesthetized with ketamine 120 mg/kg, intraper- itoneally supplemented by intravenous infusion of ketamine at 30 mg/kg/h for maintenance. Surgical preparations included cannulations of right femoral artery and vein to obtain systemic arterial pressure signals and administer anesthetic drug. A mini-laparotomy was made to facilitate the insertion of a microdialysis probe and attachment of a laser Doppler probe to the middle lobe of the liver. On experiment, L-NAME was administered via the previ-ously placed intrathecal catheter at 0, 0.37, 0.74, and 1.48 ^mol in sequence at a 2-h interval. Results : The results showed that the arterial blood pressure increased in a dose-dependent manner. By the same token, the power density of very low frequency (VLF) also increased. The low frequency (LF): high frequency (HF) ratio shifted toward parasympathetic dominance. Blood flow to the liver was unchanged except slightly decreased in the animals receiving 0.37 ^mol. The levels of monoethylglycinexylidide (MEGX), an index of hepatic metabol-ism, were unchanged throughout the experiment. Conclusions: We concluded that the blockade of spinal nitric oxide synthase by intrathecal administration of L-NAME significantly increased vasomotor tone in a dose-dependent manner and as a consequence induced a re-flex sympathetic inhibition. Hepatic microcirculation was stable with the applied doses.