title: Reversal of subarachnoid hemorrhage-induced vasoconstriction with an endothelin receptor antagonist.
abstract: Increased concentrations of the vasoconstrictor endothelin have recently been demonstrated in the cerebrospinal fluid after subarachnoid hemorrhage (SAH). This observation is consistent with the hypothesis that SAH-induced vasopasm is mediated in part by enhanced constriction due to endothelin. To investigate the issue, an endothelin receptor antagonist (ETant), cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp), was tested for its ability to reverse vasoconstriction after SAH. A transclival surgical approach to the basilar artery in rabbits was used, and the arterial diameter was measured continuously by videomicroscopy. Rabbits were divided randomly into six groups: 1) normal rabbits treated with 40 nmol/L ETant only; 2) normal rabbits treated with 50 mmol/L KCl, then 50 mmol/L KCl + 40 nmol/L ETant; 3) normal rabbits treated with 20 nmol/L endothelin-1 (ET-1), then 20 nmol/L ET-1 + 40 nmol/L ETant; 4) rabbits treated with 20 nmol/L ET-1 only; 5) rabbits subjected to SAH and treated with 40 nmol/L ETant; and 6) rabbits subjected to SAH and treated with artificial cerebrospinal fluid only. In normal (non-SAH) rabbits, ETant: 1) had little or no effect on resting tone; 2) did not reverse potassium-induced constrictions; and 3) substantially reversed endothelin-induced constrictions. The diameter of normal rabbit basilar arteries was 832.1 +/- 20.0 microns (mean +/- standard error). After SAH (double hemorrhage model), the mean diameter was 517.4 +/- 18.3 microns. The addition of ETant reversed this SAH-induced constriction by 70.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University of Virginia, Department of Neurological Surgery, Charlottesville.
authors.forename: P L
authors.initials: PL
authors.lastname: Foley
authors.forename: H H
authors.initials: HH
authors.lastname: Caner
authors.forename: N F
authors.initials: NF
authors.lastname: Kassell
authors.forename: K S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D011817:Rabbits; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin