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

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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.