Department of Nuclear Medicine, Odense University Hospital, DK-5000 Odense C, Denmark.
Acta Physiol (Oxf). 2010 Feb;198(2):125-32. doi: 10.1111/j.1748-1716.2009.02045.x. Epub 2009 Sep 24.
We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels.
Normal volunteers (23-28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) at 0.5 mg kg(-1) h(-1). One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l-NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography.
l-NAME increased MABP and total peripheral resistance (TPR, 1.02 + or - 0.05 to 1.36 + or - 0.07 mmHg s mL(-1), mean + or - SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 + or - 0.05 mmHg s mL(-1), P < 0.05). CO decreased with l-NAME (5.8 + or - 0.3 to 4.7 + or - 0.3 L min(-1), P < 0.01) and returned to control when SNP was added (6.0 + or - 0.3 L min(-1)). A decrease in plasma noradrenaline (42%, P < 0.01) during l-NAME administration was completely reversed by SNP. Plasma renin activity decreased during l-NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l-NAME and remained elevated.
Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.
我们希望将一氧化氮（NO）的水平稳定在与正常全身血液动力学相容的水平，以提供一个在没有NO水平变化的情况下研究复杂调节的模型。
正常志愿者（23-28 岁）静脉输注一氧化氮合酶（NOS）抑制剂 N（G）-硝基-L-精氨酸甲酯（l-NAME），剂量为 0.5mgkg(-1)h(-1)。1 小时后，同时输注一氧化氮供体硝普钠（SNP），剂量消除 l-NAME 的血液动力学效应。血液动力学测量包括血压（MABP）和阻抗心动图测量的心输出量（CO）。
l-NAME 增加了 MABP 和总外周阻力（TPR，1.02+或-0.05 至 1.36+或-0.07mmHg s mL(-1)，平均值+或-SEM，P<0.001）。SNP 使 TPR 下降到略低于对照的稳定值（0.92+或-0.05mmHg s mL(-1)，P<0.05）。CO 随 l-NAME 下降（5.8+或-0.3 至 4.7+或-0.3L min(-1)，P<0.01），当加入 SNP 时恢复到对照值（6.0+或-0.3L min(-1)）。l-NAME 给药期间血浆去甲肾上腺素（42%，P<0.01）下降完全被 SNP 逆转。l-NAME 给药期间血浆肾素活性下降，加入 SNP 后恢复正常。相反，血浆醛固酮升高，持续升高。
同时抑制 NOS 和给予 NO 供体可以调整 TPR 以保持在对照水平数小时。这种方法在需要稳定外周 NO 供应的方案中可能有用。然而，肾素和醛固酮分泌的分离需要进一步研究。
