Altered function of pulmonary endothelium following monocrotaline-induced lung vascular injury in rats.

1. Based on the findings in the preceding paper we investigated the ability of pulmonary endothelial cells to metabolize prostaglandin F2 alpha (PGF2 alpha) and angiotensin I (AI), and to produce endothelium-derived relaxing factor (EDRF) following lung vascular injury induced by monocrotaline in rats. The isometric tension of pulmonary artery rings isolated from rats 3-5 weeks after an injection of monocrotaline or saline was measured. For comparison the responses to drugs of the artery denuded of endothelium by rubbing were tested. 2. Acetylcholine-induced relaxation of the rings precontracted by noradrenaline was diminished in the artery from monocrotaline-treated rats, depending on the duration after treatment. The diminution was comparable to that in the control artery denuded of endothelium. 3. The contractile response to PGF2 alpha was significantly augmented in the artery injured by monocrotaline. The similar augmentation was observed after the mechanical removal of endothelium in the control artery. Decrease of EDRF was not involved in the enhancement of contractile response to PGF2 alpha in the monocrotaline-injured artery. 4. AI caused a contraction, which was sensitive to captopril, in control rings, and also in monocrotaline-injured rings to a similar degree. Removal of endothelium from the control artery did not modify the response to AI or to AII. 5. These results suggest that the monocrotaline treatment of rats suppresses the ability of pulmonary endothelium to produce EDRF and to degrade prostaglandins. The relative resistance of the AI response to endothelial injury suggests that the existence of converting enzyme is not restricted to the endothelium.