ALACEPRIL, AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, PREVENTS CEREBRAL VASOSPASM IN SUBARACHNOID HEMORRHAGE MODEL IN RATS

The effects of angiotensin-converting enzyme (ACE) inhibitors was inve stigated on the development of cerebral vasospasm and on the endotheli um-dependent relaxation in the rat subarachnoid hemorrhage (SAH) model . Alacepril or enalapril was used as an ACE inhibitor with or without a thiol moiety in the structure. SAH rats or sham-operated rats were p roduced by the injection of homologous blood or artificial cerebrospin al fluid into the cisternal magna, respectively. In the SAH rat, cereb ral vasospasm was observed at 24 h after blood injection. Acetylcholin e (Ach)-induced relaxation in basilar arteries from SAH rats significa ntly decreased compared to that from sham-operated mts, although the r elaxation induced by 3-morpholinosydnonimine, sodium nitroprusside or papaverine did not decrease. These results suggest that the endotheliu m cell function of basilar arteries in SAH rats is damaged. Alacepril prevented both the development of cerebral vasospasm and the suppressi on in the Ach-induced relaxation of basilar artery in SAH rats. Howeve r enalapril did not prevent the suppression of Ach-induced relaxation in SAH rats, despite the tendency to prevent cerebral vasospasm. There fore, it is suggested that the preventive effect of alacepril on cereb ral vasospasm could be based on its protective effect on endothelium-d ependent relaxation system.