Attenuation of SAH-induced cerebral vasospasm by a selective ECE inhibitor.
CGS 26303, a dual inhibitor of endothelin-converting enzyme-1 (ECE-1) and neutral endopeptidase 24.11, was previously shown to prevent and reverse vasospasm in an experimental model of subarachnoid hemorrhage (SAH). However, reversal of the vasospastic response was not very efficacious. This study was designed to examine the effects of a highly selective ECE-1 inhibitor, CGS 35066, on SAH-induced cerbrovasospasm. Experimental SAH was induced in New Zealand white rabbits by injecting autogenous blood into cisterna magna and CGS 35066 was injected i.v. twice daily, either at 1 h (prevention protocol) or 24 h (reversal protocol) after SAH. Treatment with CGS 35066 significantly attenuated basilar arterial narrowing at a dose of 1 mg/kg in both protocols. These findings provide support for the use of selective ECE-1 inhibitors for the treatment of SAH-induced vasospasm even after the process of arterial narrowing has begun.
Kwan
Aij-Lie
AL
Department of Neurosurgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lin
Chih-Lung
CL
Chang
Chih-Zen
CZ
Wu
Shu-Chuan
SC
Howng
Shen-Long
SL
Jeng
Arco Y
AY
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008666:Metalloendopeptidases; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control
D001572:Benzofurans; C404932:CGS 35066; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes