Tsukiyama Yoshi, Iranami Hiroshi, Kinoshita Hiroyuki, Ogawa Koji, Hatano Yoshio
Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan.
J Anesth. 2003;17(1):13-21. doi: 10.1007/s005400300003.
The present study was designed to examine the effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in rat mesenteric arterial beds perfused at a constant flow both in vitro and in situ.
In the in-vitro preparation, the mesenteric artery was cannulated and perfused (5 ml x min(-1)). The perfusion pressure was continuously monitored. Under active tone induced by methoxamine, the effects of halothane and isoflurane on the vasodilator response to acetylcholine in either the presence or absence of NG-nitro-L-arginine (L-NA), tetraethylammonium (TEA), or KCl (30 mM)-depolarization were examined. All experiments in these preparations were performed in the presence of indomethacin (10 mM). In the in-situ experimental model, rats were anesthetized with pentobarbital and the lungs were mechanically ventilated via a tracheostomy with a ventilator. The superior mesenteric artery was cannulated and used for the monitoring of the perfusion pressure. Blood shunting with constant flow (2 ml x min(-1)) from the carotid artery to the superior mesenteric artery was introduced with clamping at the immediately distal portion of the mesenteric artery branching. Following 20-min ventilation with halothane or isoflurane at 1 minimum alveolar concentration (MAC) in oxygen, acetylcholine was given from the mesenteric artery, under active tone induced by norepinephrine (100 mg x kg(-1) x hr(-1)).
In the in-vitro preparation, the nitric oxide synthase inhibitor, L-NA (100 microM) did not affect vasodilations to acetylcholine (1, 10 nM), while the K+ channel inhibitor TEA (10 mM), as well as KCl (30 mM), significantly reduced these vasodilations. However, only in the presence of L-NA, TEA and KCl completely abolished the vasodilations produced by acetylcholine. The higher concentrations of halothane (2.0%, 3.0%), but neither isoflurane (3.0%) nor the lower concentration of halothane (1.0%), significantly impaired vasodilator responses to acetylcholine in the presence of L-NA, whereas the volatile anesthetics did not affect these vasodilations in the absence of L-NA. Halothane (2.0%) did not alter the vasodilation produced by acetylcholine in the presence of TEA or KCl. In the in-vivo preparation, the vasodilator effects of acetylcholine (1 and 10 nmol) were not affected by the inhalation of halothane (1.0%) or isoflurane (1.3%).
These results suggest that, in resistance arteries in conditions of constant flow, halothane and isoflurane do not affect vasodilations in response to an endothelium-dependent agonist. However, in these preparations, once the enzymatic activity of nitric oxide synthase is inhibited, higher concentrations of halothane, but neither isoflurane nor the lower concentration of halothane, appear to impair endothelium-dependent relaxations, probably mediated by TEA-sensitive K+ channels.
本研究旨在检测氟烷和异氟烷对在体外和原位以恒定流量灌注的大鼠肠系膜动脉床中乙酰胆碱诱导的内皮依赖性血管舒张的影响。
在体外实验中，将肠系膜动脉插管并灌注（5 ml·min⁻¹）。持续监测灌注压力。在甲氧明诱导的主动张力下，检测氟烷和异氟烷在存在或不存在NG-硝基-L-精氨酸（L-NA）、四乙铵（TEA）或氯化钾（30 mM）去极化情况下对乙酰胆碱血管舒张反应的影响。这些实验均在吲哚美辛（10 mM）存在下进行。在原位实验模型中，用戊巴比妥麻醉大鼠，并通过气管切开术用呼吸机进行机械通气。将肠系膜上动脉插管用于监测灌注压力。在肠系膜动脉分支的紧邻远端进行夹闭，以实现从颈动脉到肠系膜上动脉的恒定流量（2 ml·min⁻¹）的血液分流。在氧气中以1最低肺泡浓度（MAC）用氟烷或异氟烷通气20分钟后，在去甲肾上腺素（100 μg·kg⁻¹·hr⁻¹）诱导的主动张力下，从肠系膜动脉给予乙酰胆碱。
在体外实验中，一氧化氮合酶抑制剂L-NA（100 μM）不影响对乙酰胆碱（1、10 nM）的血管舒张，而钾通道抑制剂TEA（10 mM）以及氯化钾（30 mM）显著降低这些血管舒张。然而，仅在存在L-NA、TEA和氯化钾时，乙酰胆碱产生的血管舒张才完全被消除。较高浓度的氟烷（2.0%、3.0%），但异氟烷（3.0%）和较低浓度的氟烷（1.0%）均未显著损害在存在L-NA时对乙酰胆碱的血管舒张反应，而在不存在L-NA时挥发性麻醉剂不影响这些血管舒张。氟烷（2.0%）在存在TEA或氯化钾时不改变乙酰胆碱产生的血管舒张。在体内实验中，乙酰胆碱（1和10 nmol）的血管舒张作用不受吸入氟烷（1.0%）或异氟烷（1.3%）的影响。
这些结果表明，在恒定流量条件下的阻力动脉中，氟烷和异氟烷不影响对内皮依赖性激动剂的血管舒张。然而，在这些实验中，一旦一氧化氮合酶的酶活性被抑制，较高浓度的氟烷，但异氟烷和较低浓度的氟烷均未出现，似乎会损害可能由TEA敏感钾通道介导 的内皮依赖性舒张。
