Effect of endothelinA-receptor antagonist BQ-123 and phosphoramidon on cerebral vasospasm.
The present study was designed to determine whether an endothelinA (ETA)-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 10(-8) 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 ETA-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.
Cosentino
F
F
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905.
McMahon
E G
EG
Carter
J S
JS
Katusić
Z S
ZS
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001488:Basilar Artery / Q000187:drug effects; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000134:cerebrospinal fluid; D006020:Glycopeptides / Q000627:therapeutic use*; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000503:physiopathology; D014544:Uridine Triphosphate / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D006020:Glycopeptides; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon; D014544:Uridine Triphosphate