Prevention of delayed vasospasm by an endothelin ETA receptor antagonist, BQ-123: change of ETA receptor mRNA expression in a canine subarachnoid hemorrhage model.
The authors investigated the roles of endothelin (ET)-1 and the ETA receptor in the pathogenesis of delayed cerebral vasospasm following subarachnoid hemorrhage (SAH). A study was made of the preventive effect of a novel ETA receptor antagonist, BQ-123, on vasospasm and the expression of the ETA receptor messenger ribonucleic acid (mRNA) using a canine two-hemorrhage SAH model. Continuous intrathecal administration of BQ-123 (5 x 10(-6) mol/day) prevented narrowing of the basilar artery on Day 7 after SAH in 97.6% of cases in the study group versus 70.7% of cases in the control group (p < 0.05). While expression of the mRNA-coding ETA receptor was not detected in the control animals, it markedly increased on Day 3 after SAH and was also detected on Day 7. The results suggest that endothelin-1 and the ETA receptor participate in the pathogenesis of delayed cerebral vasospasm following SAH.
Itoh
S
S
Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan.
Sasaki
T
T
Asai
A
A
Kuchino
Y
Y
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D015152:Blotting, Northern; D003329:Coronary Vasospasm / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015342:DNA Probes; D018076:DNA, Complementary; D004195:Disease Models, Animal; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics*; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000235:genetics*; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000235:genetics
D015342:DNA Probes; D018076:DNA, Complementary; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)