Possible involvement of neuronal nitric oxide synthase enzyme in early-phase isoflurane-induced hypotension in rats.
Possible involvement of neuronal nitric oxide synthase enzyme in early-phase isoflurane-induced hypotension in rats.
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DOI：
10.1016/j.lfs.2004.04.059
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发表时间：
2004-12
期刊：
影响因子：
6.1
通讯作者：
E. A. Ellenberger;H. L. Lucas;Janet L. Mueller;P. L. Barrington;Eunhee Chung;Y. Ohgami;R. Quock
中科院分区：
文献类型：
--
作者：
E. A. Ellenberger;H. L. Lucas;Janet L. Mueller;P. L. Barrington;Eunhee Chung;Y. Ohgami;R. Quock
本研究旨在证实一氧化氮合酶（NOS）参与异氟醚诱导的早期低血压，并确定NOS是神经型NOS（nNOS）还是内皮型NOS（eNOS）。平均动脉压（MAP）直接测量从股动脉麻醉大鼠。在用溶剂或以下NOS抑制剂之一预处理后的大鼠中监测异氟烷诱导的MAP变化：L-NG-单甲基-L-精氨酸（L-NMMA），其是非选择性的; L-NG-硝基精氨酸（L-NOARG），其对nNOS和eNOS更具选择性;和7-硝基吲唑（7-NI），其对nNOS具有选择性。暴露于含2%异氟烷的氧气中可使MAP出现三阶段性降低，包括平均动脉压（MAP）在最初2½ min内下降25-30%的早期阶段。通过静脉注射L-NMMA或L-NOARG预处理可消除这种早期水肿反应，但随后的阶段不会。腹腔注射7-NI预处理也显著减弱了早期低血压;然而，阻滞不如L-NMMA或L-NOARG完全。从溶剂和7-NI预处理的大鼠中取出小脑和主动脉，并通过测定[14 C] L-精氨酸向[14 C] L-瓜氨酸的转化来测定NOS活性。7-NI预处理显着降低了小脑的NOS活性，但没有降低主动脉的NOS活性。这些结果表明，异氟醚诱导的早期低血压可能涉及nNOS以及eNOS。nNOS可能参与异氟烷诱导的神经元释放内源性阿片肽的调节，其产生依赖于来自eNOS作用的NO的血管舒张。
This study was conducted to demonstrate the involvement of nitric oxide synthase (NOS) in the early-phase isoflurane-induced hypotension and to ascertain whether this NOS is neuronal NOS (nNOS) or endothelial NOS (eNOS). Mean arterial pressures (MAPs) were directly measured from the femoral arteries of urethane-anesthetized rats. Isoflurane-induced changes in MAP were monitored in rats following pretreatment with vehicle or one of the following NOS inhibitors: L-NG-monomethyl-L-arginine (L-NMMA), which is non-selective; L-NG-nitro arginine (L-NOARG), which is more selective for nNOS and eNOS; and 7-nitroindazole (7-NI), which is selective for nNOS. Exposure to 2% isoflurane in oxygen produced a triphasic reduction in MAP, including an early phase in which mean arterial pressure (MAP) fell by 25-30% during the initial 2½ min. This early hypotensive response, but not subsequent phases, was abolished by i.v. pretreatment with either L-NMMA or L-NOARG. The early-phase hypotension was also significantly attenuated by i.p. pretreatment with 7-NI; however, the blockade was not as complete as with L-NMMA or L-NOARG. Cerebella and aorta were removed from vehicle- and 7-NI pretreated rats and assayed for NOS activity by determining the conversion of [14C]L-arginine to [14C]L-citrulline. The 7-NI pretreatment significantly reduced NOS activity in the cerebellum but not the aorta. These findings indicate that the early-phase isoflurane-induced hypotension may involve nNOS as well as eNOS. The nNOS may participate in regulation of isoflurane-induced neuronal release of endogenous opioid peptide, which produces a vasodilation that is dependent on NO derived from an action of eNOS.