Abstract
The present study was designed to determine whether an endothelin(A) (ET(A))-receptor antagonist BQ-123 (cyclo[Dtrp, Dasp, pro-D-Val-Leu]) or an ET-converting enzyme inhibitor phosphoramidon may prevent development of cerebral vasospasm after subarachnoid hemorrhage (SAH). A 'double hemorrhage' canine model of the disease was used (n = 17 dogs), and the degree of vasospasm of the basilar artery was assessed by angiography. Mongrel dogs of either sex were divided into three experimental groups: animals treated with daily intracisternal injections of BQ-123 (10-4 M; n = 6) or phosphoramidon (2 x 10-4 M; n = 6) and control animals treated with saline solution (n = 5). Diameter of basilar arteries in animals treated with saline solution was reduced by SAH to 56 ± 7% of control diameter. BQ-123 and phosphoramidon did not significantly affect SAH-induced vasospasm (diameters were 62 ± 0% and 56 ± 10% of control diameters for BQ-123 and phosphoramidon, respectively). In contrast, in isolated canine basilar arteries BQ-123 (10-5 M) selectively inhibited concentration-dependent contractions to ET-1 (10- 11-3 x 108 M; n = 5). Levels of immunoreactive ET in plasma and cerebrospinal fluid were not affected by development of vasospasm. These results suggest that intracisternal injections of ET(A)-receptor antagonist or phosphoramidon cannot prevent SAH-induced cerebral vasospasm and that ET- 1 may not be the major mediator responsible for the decrease in cerebral arterial diameter associated with SAH.
Original language | English (US) |
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Pages (from-to) | S332-S335 |
Journal | Journal of Cardiovascular Pharmacology |
Volume | 22 |
Issue number | SUPPL. 8 |
DOIs | |
State | Published - 1993 |
Keywords
- BQ- 123
- Cerebral vasospasm
- Endothelin(A) receptor
- Phosphoramidon
- Subarachnoid hemorrhage
ASJC Scopus subject areas
- Pharmacology
- Cardiology and Cardiovascular Medicine