Ikeda S, Shirai M, Shimouchi A, Min K Y, Ohsawa N, Ninomiya I
Departments of Cardiac Physiology and Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Suita, 565-0873, Japan.
Jpn J Physiol. 1999 Feb;49(1):89-98. doi: 10.2170/jjphysiol.49.89.
Using an X-ray television system on anesthetized cats, we directly measured internal diameter (ID) changes in identical small pulmonary vessels (100-1,100 microm ID) in response to inhalations of 25, 250, and 2,500 ng/kg/min aerosolized prostacyclin (PGI2), 4 and 34 ppm nitric oxide (NO), and the combination of aerosolized PGI2 and NO. We also compared ID changes during 250 ng/kg/min PGI2 inhalation both with and without an Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg I.V.) pretreatment. In the arteries, inhaled PGI2 increased 100-900 microm vessel ID in a dose-dependent manner but caused no significant, or only slight, ID increases in the vessels larger than this. The greatest ID increase ( approximately 22%) was in the 100-500 microm arteries in response to 2,500 ng/kg/min PGI2 inhalation. PGI2 also increased the ID of the veins (6-12%), but the results were not dose related. NO inhalation also resulted in non-uniform ID response patterns similar to PGI2 with no significant, or only minimal, ID increases of the arteries >900 microm. The simultaneous inhalation of 2,500 ng/kg/min PGI2 and 34 ppm NO increased the arterial ID (maximum approximately 34%) more than either drug alone and to almost the same extent as brought about by injected papaverine (2 mg/kg), a smooth muscle relaxant. Inhaled PGI2 (250 ng/kg/min) decreased pulmonary arterial pressure and increased arterial ID to nearly the same extent with or without L-NAME pretreatment. These results indicate that inhaled PGI2 and inhaled NO locally dilate 100-900 microm pulmonary arteries in a dose-dependent manner and with a similar ID response pattern, and that the combination of these drugs produces a more enhanced vasodilator effect compared to their separate effects and induces the maximum dilated states. The data also suggest that inhaled PGI2 dilates these arteries directly, rather than via secondary release of endogenous NO.
在麻醉猫身上使用X射线电视系统，我们直接测量了相同的小肺血管（内径100 - 1100微米）在吸入25、250和2500纳克/千克/分钟雾化前列环素（PGI2）、4 ppm和34 ppm一氧化氮（NO）以及雾化PGI2与NO组合后的内径（ID）变化。我们还比较了在吸入250纳克/千克/分钟PGI2时，有无Nω-硝基-L-精氨酸甲酯（L-NAME，30毫克/千克静脉注射）预处理情况下的内径变化。在动脉中，吸入的PGI2以剂量依赖性方式增加100 - 900微米血管的内径，但对大于此内径的血管无显著或仅有轻微的内径增加。吸入2500纳克/千克/分钟PGI2时，100 - 500微米动脉的内径增加最大（约22%）。PGI2也增加了静脉的内径（6 - 12%），但结果与剂量无关。吸入NO也导致了与PGI2类似的内径反应模式不均匀，对于内径大于900微米的动脉，内径无显著增加或仅有最小增加。同时吸入2500纳克/千克/分钟PGI2和34 ppm NO使动脉内径增加（最大约34%），比单独使用任何一种药物都更多，且几乎达到与注射平滑肌松弛剂罂粟碱（2毫克/千克）相同的程度。吸入PGI2（250纳克/千克/分钟）降低肺动脉压并增加动脉内径，无论有无L-NAME预处理，增加程度几乎相同。这些结果表明，吸入的PGI2和吸入的NO以剂量依赖性方式局部扩张100 - 900微米的肺动脉，且内径反应模式相似，并且与单独使用相比，这两种药物的组合产生更强的血管舒张作用并诱导最大扩张状态。数据还表明，吸入的PGI2直接扩张这些动脉，而非通过内源性NO的二次释放。
