Inhibition of nitric oxide synthase evokes central sympatho-excitation in healthy humans.
Inhibition of nitric oxide synthase evokes central sympatho-excitation in healthy humans.
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一氧化氮合酶的抑制会引起健康人的中枢交感神经兴奋。
DOI：
10.1113/jphysiol.2009.177204
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Fadel,PaulJ
中科院分区：
文献类型：
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作者：
Young,ColinN;Fisher,JamesP;Gallagher,KevinM;Whaley-Connell,Adam;Chaudhary,Kunal;Victor,RonaldG;Thomas,GailD;Fadel,PaulJ
动物研究表明，一氧化氮是一个关键的信号分子参与紧张性抑制中枢交感神经流出脑干。将这些发现扩展到人类是困难的，因为全身输注一氧化氮合酶（NOS）抑制剂由于抑制内皮NOS而增加血压，导致动脉压力感受器反射的激活和随后的中枢交感神经流出的抑制。为了克服压力感受器反射的这种混杂抑制影响，在当前的研究中，我们直接测量皮肤交感神经活动（SNA），这是不受压力感受器控制。在NOS抑制剂或NG-硝基-L-精氨酸甲酯（l-NAME; 4 mg kg-1）静脉输注前、输注60分钟期间以及输注后120分钟（即总共180分钟），对健康血压正常的人进行了研究。连续测量皮肤SNA和动脉血压（BP）。在thel-NAME输注结束时，BP从基线升高（Δ14 ± 2 mmHg;P< 0.05），并在实验的剩余时间内保持显著升高（Δ18 ± 3 mmHg;P< 0.05）。类似地，全身性NOS抑制产生皮肤SNA的时间依赖性增加，使得皮肤SNA在thel-NAME输注结束时升高（总活性，200 ± 22%基线;P= 0.08），并且在研究方案结束时进一步增加（总活性，350 ± 41%基线;P< 0.05）。重要的是，皮肤SNA在时间和高血压（苯巴比妥）对照实验期间保持不变。这些发现表明，NOS的药理学抑制引起交感神经激活，并支持一氧化氮在人类中枢交感神经控制中的作用。
Animal studies have indicated that nitric oxide is a key signalling molecule involved in the tonic restraint of central sympathetic outflow from the brainstem. Extension of these findings to humans has been difficult because systemic infusion of nitric oxide synthase (NOS) inhibitors increases blood pressure due to inhibition of endothelial NOS, resulting in activation of the arterial baroreflex and subsequent inhibition of central sympathetic outflow. To overcome this confounding inhibitory influence of the baroreflex, in the current study we directly measured skin sympathetic nerve activity (SNA), which is not under baroreceptor control. Healthy, normotensive humans were studied before, during a 60 min intravenous infusion of the NOS inhibitorNG‐nitro‐l‐arginine methyl ester (l‐NAME; 4 mg kg−1), and for 120 min following the infusion (i.e. 180 min total). Skin SNA and arterial blood pressure (BP) were continuously measured. BP was increased from baseline at the end of thel‐NAME infusion (Δ14 ± 2 mmHg;P< 0.05) and remained significantly elevated for the remainder of the experiment (Δ18 ± 3 mmHg;P< 0.05). Similarly, systemic NOS inhibition produced time‐dependent increases in skin SNA, such that skin SNA was elevated at the end of thel‐NAME infusion (total activity, 200 ± 22% baseline;P= 0.08) and was further increased at the end of the study protocol (total activity, 350 ± 41% baseline;P< 0.05). Importantly, skin SNA remained unchanged during time and hypertensive (phenylephrine) control experiments. These findings indicate that pharmacological inhibition of NOS causes sympathetic activation and support a role of nitric oxide in central sympathetic control in humans.