Alacepril, an angiotensin-converting enzyme inhibitor, prevents cerebral vasospasm in subarachnoid hemorrhage model in rats.
The effects of angiotensin-converting enzyme (ACE) inhibitors was investigated on the development of cerebral vasospasm and on the endothelium-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 produced by the injection of homologous blood or artificial cerebrospinal fluid into the cisternal magna, respectively. In the SAH rat, cerebral vasospasm was observed at 24 h after blood injection. Acetylcholine (Ach)-induced relaxation in basilar arteries from SAH rats significantly decreased compared to that from sham-operated rats, although the relaxation induced by 3-morpholinosydnonimine, sodium nitroprusside or papaverine did not decrease. These results suggest that the endothelium cell function of basilar arteries in SAH rats is damaged. Alacepril prevented both the development of cerebral vasospasm and the suppression in the Ach-induced relaxation of basilar artery in SAH rats. However, enalapril did not prevent the suppression of Ach-induced relaxation in SAH rats, despite the tendency to prevent cerebral vasospasm. Therefore, it is suggested that the preventive effect of alacepril on cerebral vasospasm could be based on its protective effect on endothelium-dependent relaxation system.
Honda
Y
Y
Department of Pharmacology I, Dainippon Pharmaceutical, Co., Ltd., Osaka, Japan.
Minato
H
H
Fujitani
B
B
Masuda
Y
Y
Hosoki
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D002216:Captopril; D000109:Acetylcholine; C046835:alacepril