NO production by cNOS and iNOS reflects blood pressure changes in LPS-challenged mice
NO production by cNOS and iNOS reflects blood pressure changes in LPS-challenged mice
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DOI：
10.1152/ajpendo.00004.2002
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发表时间：
2003-10-01
影响因子：
5.1
通讯作者：
Deutz, NEP
中科院分区：
文献类型：
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作者：
Hallemeesch, MM;Janssen, BJA;Deutz, NEP
一氧化氮（NO）的产生增加是脓毒症期间低血压和休克的原因。在本实验中，我们测量了基线条件下和LPS处理（100杯/10克LPS）下小鼠内皮(e)和诱导(i)一氧化氮合酶（NOS）对全身一氧化氮生成的贡献。通过L-[胍- n -15(2)]精氨酸转化为L-[尿素- n -15]瓜氨酸的速率来测量NO合成，并通过比较enos缺陷[(-/-)]和iNOS（-/-）小鼠与野生型（WT）小鼠的NO生成来评估特定NOS亚型的贡献。在基线条件下，WT和iNOS（-/-）小鼠的NO产量相似，但eNOS（-/-）小鼠的NO产量较低[WT: 1.2+/-0.2；伊诺(- / -):1.2 + / - -0.2;eNOS(-/-): 0.6+/-0.3 nmol10g体wt(-1).min(-1)]。在LPS刺激下（5 h）， WT和eNOS（-/-）小鼠的系统NO产量增加，而iNOS（-/-）小鼠的系统NO产量下降[WT: 2.7+/-0.3；以挪士(- / -):2.2 + / - -0.6;iNOS(-/-): 0.7+/-0.1 nmol10g体wt(-1).min(-1)]。LPS处理5小时后，WT小鼠的血压下降了14 mmHg，而iNOS（-/-）小鼠的血压没有下降。目前的研究结果提供了确凿的证据，表明在用细菌LPS处理后，NO产量的增加完全依赖于iNOS，而由cNOS介导的NO产量减少。此外，数据显示lps诱导的血压反应依赖于iNOS。
Increased nitric oxide (NO) production is the cause of hypotension and shock during sepsis. In the present experiments, we have measured the contribution of endothelial (e) and inducible (i) nitric oxide synthase (NOS) to systemic NO production in mice under baseline conditions and upon LPS treatment (100 mug/10 g ip LPS). NO synthesis was measured by the rate of conversion of L-[guanidino-N-15(2)] arginine to L-[ureido-N-15] citrulline, and the contribution of the specific NOS isoforms was evaluated by comparing NO production in eNOS-deficient [(-/-)] and iNOS(-/-) mice with that in wild-type (WT) mice. Under baseline conditions, NO production was similar in WT and iNOS(-/-) mice but lower in eNOS(-/-) mice [WT: 1.2+/-0.2; iNOS(-/-): 1.2+/-0.2; eNOS(-/-): 0.6+/-0.3 nmol.10 g body wt(-1).min(-1)]. In response to the challenge with LPS ( 5 h), systemic NO production increased in WT and eNOS(-/-) mice but fell in iNOS(-/-) mice [WT: 2.7+/-0.3; eNOS(-/-): 2.2+/-0.6; iNOS(-/-): 0.7+/-0.1 nmol.10 g body wt(-1).min(-1)]. After 5 h of LPS treatment, blood pressure had dropped 14 mmHg in WT but not in iNOS(-/-) mice. The present findings provide firm evidence that, upon treatment with bacterial LPS, the increase of NO production is solely dependent on iNOS, whereas that mediated by cNOS is reduced. Furthermore, the data show that the LPS-induced blood pressure response is dependent on iNOS.