Hypoventilation and elevation of end-expiratory pressure release a substance which relaxes isolated arteries and disaggregates platelets in the presence of cyclooxygenase inhibitors.

A prostacyclin-like substance was detected by bioassay in the blood of dogs and cats during hypoventilation and increased end-expiratory pressure. This biologically active material, most likely originating from lungs, relaxed isolated vascular strips and disaggregated platelets. Its release was not prevented by indomethacin or aspirin. Biological activity was not abolished by 10 min incubation of blood at 38 degrees C. Although the identity of the substance has not been established the release of a biologically active prostacyclin-like material might play a role in circulatory adaptation to disturbed ventilatory function.

Effect of prostaglandin E2 and of indomethacin upon cerebral and pulmonary consequences of exposure to hyperbaric oxygen in rats.

There are few data in the literature suggesting that endogenous prostaglandins (PGs) might be involved in the pathomechanism of seizures. Since the mechanism of seizures inducted by exposure to oxygen high pressure (OHP) is not fully elucidated, this study was designed to investigate the effect of exogenous PG s and of indomethacin (a Pg synthesis inhibitor) upon the development and consequences of seizures in rats exposed to OHP (5 ata). In the animals pretreated with PGE2 (1 ng/kg s.c.) pre-seizure time was shortened, lung weight : body weight index increased and symptoms of respiratory failure potentiated, as compared with the control group. Indomethacin (5 mg/kg i.p) prevented the development of seizures and of pulmonary consequences of OHP exposure. Biochemical examination of brains has shown that velocity of free radical oxidation of lipids (reactions manifested by the breakdown of phospholipid fatty acids, mainly unsaturated ones) enhanced by OHP exposure, is further potentiated in rats pretreated with PGE2. Electron microscopic study has shown the alterations similar to those seen in brain ischemia and/or hypoxia, and the magnitude of changes was related to the intensity of symptoms evoked by OHP. The results show that cerebral and pulmonary consequences of OHP exposure are potentiated by exogenous PGE2 and prevented by inhibition of endogenous PG synthesis. This suggests that PGs and/or their active metabolites might be involved in the mechanism of oxygen toxicity during exposure to hyperbaric oxygen.

Inhibitory effect of hydrocortisone on the release of prostaglandins from dog's brain in hypoxia and cerebral embolism.

Cerebral hypoxia and embolism evoke the release of prostaglandin (PG)-like substances, predominantly of E type, into cerebral venous blood. This has been shown by bioassay used for monitoring the level of PG-like substances in sagittal sinus blood (ssb) in dogs. Hypoxia was induced by inhalation of 8% O2 in N2, embolism by an injection of air into internal carotid artery. This led to an increase in the level of PG-like substances in ssb, with no detectable change in the concentration of PGs in peripheral venous blood, indicating that PGs detected in ssb originate from cerebral venous outflow. The output amounted 6 ng/ml (in PGE2 equivalents). Hydrocortisone (HC) in a dose of 30 mg/kg suppressed the release of PG-like substances induced by either hypoxia or embolism. These results were confirmed by radioimmunoassay of PGs in ssb. Plasma levels of PGs E and F2 alpha were elevated following cerebral embolism as compared to initial values and greatly suppressed by HC administration. Suppression of PG formation by HC in this experimental system seems to be related to the membrane--stabilizing action of this hormone. This is of interest in view of the usefulness of steroid therapy in cerebrovascular pathology.