1. Prevention of subarachnoid hemorrhage-induced cerebral vasospasm by oral administration of endothelin receptor antagonists
- Author
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Robert M. Rapoport, Hussein Hallak, Mario Zuccarello, Volker Breu, Giovanni B. Soattin, and Adam I. Lewis
- Subjects
Endothelin Receptor Antagonists ,Male ,Subarachnoid hemorrhage ,medicine.drug_class ,Administration, Oral ,Dioxoles ,Pharmacology ,Cerebrospinal fluid ,Cerebral vasospasm ,Oral administration ,medicine ,Animals ,Sulfonamides ,Endothelin receptor antagonist ,business.industry ,Bosentan ,Subarachnoid Hemorrhage ,medicine.disease ,Receptor antagonist ,Ischemic Attack, Transient ,Vasoconstriction ,Anesthesia ,Basilar Artery ,Rabbits ,Endothelin receptor ,business ,medicine.drug - Abstract
✓ The purpose of this study was to investigate the effectiveness of oral treatment with the endothelin (ET)A/B receptor antagonist Ro 47-0203, 4-tert-butyl-N-[6-(hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2′-bipyrimidin-4-yl]-benzenesulfonamide (bosentan), and the ETA receptor antagonist 2-benzo[1,3]dioxol-5-yl-3-benzyl-4-(4-methoxy-phenyl)-4-oxobut-2-enoic acid monosodium salt (PD155080), in the prevention of subarachnoid hemorrhage (SAH)—induced delayed cerebral vasospasm. Double hemorrhage in the rabbit constricted the basilar artery to 34% of control as determined by angiography. Oral bosentan and PD155080 administration after the initial SAH decreased the magnitude of constriction to 9% and 16% of control, respectively. Plasma and cerebrospinal fluid bosentan levels and plasma PD155080 levels were consistent with concentrations reported to inhibit ET-1 constriction of blood vessels in vitro. These results support the use of oral administration of ETA/B and ETA receptor antagonists as potential specific treatment for vasospasm resulting from SAH in humans.
- Published
- 1996