Studies on the alterations of lung endothelial cells and the metabolism of autacoids during lung diseases

为了解肺血管损伤如何影响血管活性自育素的代谢功能，用野百合碱（monocrotaline，monocrotaline）致大鼠肺血管损伤，3 ~ 5周后观察肺内皮细胞变性或坏死。当从i. v.和i.a.反应的差异来评价自他类化合物在肺中的代谢时，结果<E_2>表明，在单百合碱诱导的肺损伤过程中，前列腺素（PG）的降解受到抑制，而血管紧张素<I>（A<I>）向血管紧张素<II>（A<II>）的转化和缓激肽的降解不受影响。乙酰胆碱诱导的去甲肾上腺素预收缩环的舒张在野百合碱损伤的动脉中被抑制，表明在肺血管损伤期间内皮源性舒张因子（EDRF）的产生减少。在野百合碱损伤的动脉和摩擦去内皮化的动脉中，&lt;PGF_（2&gt; α &lt;）&gt;引起的收缩作用均增强。这种增强被认为是由于内皮细胞对PG的降解减少。另一方面，A的转换<I>并没有改变内皮损伤，因为A<I>可能被转换为A<II>的酶存在于其他网站比内皮。犬和牛的肺动脉内皮细胞具有与大鼠相似的特征，提示肺血管损伤可使EDRF的产生减少，从而引起肺动脉高压，并可能通过降低肺内皮细胞PGs代谢而改变肺和全身血流动力学及水电解质平衡。

To learn how lung vascular injury alters the function to metabolize vaso-active autacoids, lung vascular lesions were produced in rats by a single injection of monocrotaline.Three to five weeks after the injection the degeneration or necrotization of lung endothelial cells was observed. When the metabolism of autacoids in lung was evaluated from the difference of responses to i.v. and i.a. injections of substances, the degradation of prostaglandin (PG) <E_2> was suppressed during the monocrotaline-induced lung injury, while the conversion of angiotensin- <I> (A <I> ) to angiotensin- <II> (A <II> ) and the degradation of bradykinin were unaffected.In the next experiments, the effects of autacoids on the mechanical property of pulmonary artery rings isolated from control and monocrotaline-treated rats were examined. Acetylcholine-induced relaxation of rings precontracted by noradrenaline was suppressed in monocrotaline-injured artery suggesting that the production of endothelium-derived relaxing factor (EDRF) is decreased during lung vascular injury. The contraction induced by <PGF_(2> alpha <)> was enhanced in either monocrotaline-injured artery or de-endothelialized artery by rubbing. This enhancement was considered to be due to decreased degradation of PG by endothelial cells. On the other hand, the conversion of A <I> was not altered by endothelial injury because A <I> was probably converted to A <II> by the enzyme present in other sites than endothelium. Canine and bovine pulmonary artery endothelium showed the characteristics similar to that of rats.It is suggested that lung vascular injury impaires the production of EDRF, which may cause pulmonary hypertension, and that the injury may alter the pulmonary and systemic hemodynamics and fluid-electrolyte balance as a result of decreased metabolism of PGs in pulmonary endothelium.