吸入一氧化氮治疗肺动脉高压的作用机理与应用评价

目的对吸入一氧化氮（NO）治疗肺动脉高压的临床药理学与临床毒理学进行评价。方法30例成人和54例儿童肺动脉高压患者吸人NO治疗。吸入前、吸入后30min和停吸后2h、24h分别取血浆测定NO代谢产物（NO_2~-）的浓度以及环磷酸鸟苷（cGMP）、丙二醛（MDA）和内皮素（ET-1）的水平，取循环白细胞测定一氧化氮合成酶（NOS）的活性。结果吸入NO后血中一氧化氮的浓度明显增加（P＜0．01），信息传递物质cGMP水平显著升高（P＜0．05），而脂质过氧化代谢产物MDA没有增多（p＞0．05），ET-1水平保持不变（P＞0．05），NOS活性不受影响（P＞0．05）。结论外源性NO亦通过cGMP发挥作用。当吸入浓度维持在一定范围内时，NO作为药物治疗是基本安全、有效的，因此NO是一种极具潜力的选择性肺动脉扩张剂。

Mechaism of treating pulmonary hypertension by Inhaling nitric oxide and its use

Objective To evaluate the pharmacological and toxicological effects by inhaling nitric oxide (NO) for treating pulmonary hyperten sion. Methods Pulmonary hypertension was teat ed by inhaling nitric oxide in 30 adult and 54 child Patients. Blood samples were collected before inhaling NO, 30 min following inhalation of NO, and 2 hand 24 h afther stopped the inhalation. The plasma samples were used to measure the concentrations of nitrite (NO_2~-), guanosine 3', 5' -cyclic phosphate (cGMP), malonaldehyde (MDA) and endothelin 1. The white cells were used to detetmine the activity of nitric oxide synthase (NOS). Results After inhaling NO, the plasma concentrations of NO metabolite (NO_2~- ) increased obviously (P < 0.01),plasma levels of the signal messenger cGMP went up significantly (P < 0.05), but the lipoperoxide metabolite MDA did not increase (P > 0.05 ), theendothelin -1 kept the previous levels (P > 0.05),and the NOS activity was not affected (P > 0.05) inboth adult and child patients. Conclusion vasodilation of inhaling NO was transmitted by cGMP.When the inhalation concentaions were maintainedonional (such as less than 80PPm), NO asding is basically safe and effective. Therefore, NOis a alternative potenhal bang for Pulmomp vasodlation.