Kiely D G, Lee A F, Struthers A D, Lipworth B J
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
Br J Clin Pharmacol. 1998 Sep;46(3):263-6. doi: 10.1046/j.1365-2125.1998.00767.x.
The aim of this study was to examine whether nitric oxide (NO) has an important role in maintaining basal vascular tone in normal man by examining the effects of nitric oxide inhibition using N(G)-monomethyl-L-arginine (L-NMMA) on systemic and pulmonary haemodynamics.
Ten normal male volunteers 26 +/- 1.6 years were studied on two separate occasions in a double-blind, placebo controlled crossover study. They were randomised to receive either a continuous infusion of L-NMMA (4 mg kg(-1) h(-1)) with a front loaded bolus (4 mg kg(-1)) or volume matched placebo. Pulsed wave Doppler echocardiography was used to measure cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic vascular resistance (SVR) and total pulmonary vascular resistance (TPR). Measurements were made prior to infusion (t0) and after 4, 8, and 12 min (t1, t2 and t3).
Infusion of L-NMMA significantly increased mean arterial blood pressure (MAP), SVR and TPR and significantly reduced heart rate (HR), stroke volume (SV) and CO compared to placebo. These effects were observed at t1 and persisted during the entire infusion period.
These results are consistent with a role for basal nitric oxide generation in the maintenance of basal systemic and pulmonary vascular tone in normal man.
本研究旨在通过检测使用N(G)-单甲基-L-精氨酸(L-NMMA)抑制一氧化氮对全身和肺血流动力学的影响,来研究一氧化氮(NO)在维持正常男性基础血管张力方面是否具有重要作用。
在一项双盲、安慰剂对照的交叉研究中,对10名年龄为26±1.6岁的正常男性志愿者分两次进行研究。他们被随机分为接受持续输注L-NMMA(4mg·kg⁻¹·h⁻¹)并给予负荷剂量(4mg·kg⁻¹)或等容量的安慰剂。使用脉冲波多普勒超声心动图测量心输出量(CO)、平均肺动脉压(MPAP),从而计算全身血管阻力(SVR)和总肺血管阻力(TPR)。在输注前(t0)以及输注4、8和12分钟后(t1、t2和t3)进行测量。
与安慰剂相比,输注L-NMMA显著增加平均动脉血压(MAP)、SVR和TPR,并显著降低心率(HR)、每搏输出量(SV)和CO。这些效应在t1时出现,并在整个输注期间持续存在。
这些结果与基础一氧化氮生成在维持正常男性基础全身和肺血管张力中发挥作用相一致。