Herity N A, Allen J D, Silke B, Adgey A A
Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, United Kingdom.
Cardiovasc Res. 1994 Jun;28(6):894-900. doi: 10.1093/cvr/28.6.894.
The aim was to test the ability of levcromakalim, a potassium channel opener, and sodium nitroprusside, a nitric oxide donor, to reverse the systemic and pulmonary vasoconstrictor actions of NG-nitro-L-arginine methyl ester (L-NAME), and thus to restore cardiac output in anaesthetised pigs.
In separate groups of pigs administration of a bolus of L-NAME (10 mg.kg-1) was followed either by no further agent (control group; n = 8) or by increasing bolus doses of levcromakalim (10, 20, and 40 micrograms.kg-1; n = 8) or by increasing infused doses of sodium nitroprusside (1, 2, and 4 micrograms.kg-1.min-1 for 15 min at each dose). The same doses of levcromakalim and sodium nitroprusside were also given to pigs (n = 6 in each group) which had been pretreated with saline rather than L-NAME. The changes in systemic and pulmonary haemodynamic indices and cardiac output as a result of each intervention were measured at each stage and compared between and within drug groups.
In each group, the bolus of L-NAME caused increases in systemic vascular resistance, mean arterial pressure, pulmonary vascular resistance, and mean pulmonary artery pressure, and a reduction in cardiac output. These effects were significantly different from pretreatment values at 15 min, and were maintained for at least 60 min when no further agent was given. The subsequent administration of levcromakalim caused significant reductions in systemic vascular resistance and mean arterial pressure, the effects being greater than in animals that had been pretreated with saline rather than L-NAME. Pulmonary vascular resistance and mean pulmonary artery pressure were also reduced, but to a lesser degree. Cardiac output was partially but significantly restored. The subsequent administration of sodium nitroprusside caused significant reductions in systemic vascular resistance, mean arterial pressure, pulmonary vascular resistance, and mean pulmonary artery pressure. These effects were significantly greater than those in animals that had been pretreated with saline rather than L-NAME. Cardiac output was weakly, though significantly restored.
Increased systemic vascular resistance following a bolus of L-NAME (10 mg.kg-1) is reversed by subsequent administration of levcromakalim (10-40 micrograms.kg-1) or sodium nitroprusside (1-4 micrograms.kg-1.min-1) associated with partial restoration of cardiac output. The degree to which cardiac output is restored by these two agents is limited by a concomitant reduction in preload.
旨在测试钾通道开放剂左卡尼汀和一氧化氮供体硝普钠逆转 NG-硝基-L-精氨酸甲酯（L-NAME）的全身和肺血管收缩作用的能力，从而恢复麻醉猪的心输出量。
在不同组的猪中，静脉注射一剂 L-NAME（10 mg·kg-1）后，一组不再给予其他药物（对照组；n = 8），另一组给予递增剂量的静脉推注左卡尼汀（10、20 和 40 μg·kg-1；n = 8），第三组给予递增剂量的硝普钠静脉输注（1、2 和 4 μg·kg-1·min-1，每种剂量持续 15 分钟）。相同剂量的左卡尼汀和硝普钠也给予用生理盐水而非 L-NAME 预处理过的猪（每组 n = 6）。在每个阶段测量每次干预后全身和肺血流动力学指标及心输出量的变化，并在药物组之间和组内进行比较。
在每组中，一剂 L-NAME 导致全身血管阻力、平均动脉压、肺血管阻力和平均肺动脉压升高，心输出量降低。这些效应在 15 分钟时与预处理值有显著差异，在不再给予其他药物时至少维持 60 分钟。随后给予左卡尼汀导致全身血管阻力和平均动脉压显著降低，其效应大于用生理盐水而非 L-NAME 预处理过的动物。肺血管阻力和平均肺动脉压也降低，但程度较小。心输出量部分但显著恢复。随后给予硝普钠导致全身血管阻力、平均动脉压、肺血管阻力和平均肺动脉压显著降低。这些效应显著大于用生理盐水而非 L-NAME 预处理过的动物。心输出量虽微弱但显著恢复。
静脉注射一剂 L-NAME（10 mg·kg-1）后增加的全身血管阻力可通过随后给予左卡尼汀（10 - 40 μg·kg-1）或硝普钠（1 - 4 μg·kg-1·min-1）而逆转，同时心输出量部分恢复。这两种药物恢复心输出量的程度受到前负荷同时降低的限制。
