Prevention of subarachnoid hemorrhage—induced cerebral vasospasm by oral administration of endothelin receptor antagonists

Restricted access

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

✓ 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.

Article Information

Contributor Notes

Address reprint requests to: Mario Zuccarello, M.D., University of Cincinnati, College of Medicine, P.O. Box 670515, Cincinnati, Ohio 45267–0515.
Headings
References
  • 1.

    Breu VLöffler BMClozel M: In vitro characterization of Ro 46-2005, a novel synthetic non-peptide endothelin antagonist of ETA and ETB receptors. FEBS Lett 334:2102141993Breu V Löffler BM Clozel M: In vitro characterization of Ro 46-2005 a novel synthetic non-peptide endothelin antagonist of ETA and ETB receptors. FEBS Lett 334:210–214 1993

    • Search Google Scholar
    • Export Citation
  • 2.

    Clozel MBreu VBurri Ket al: Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature 365:7597611993Clozel M Breu V Burri K et al: Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature 365:759–761 1993

    • Search Google Scholar
    • Export Citation
  • 3.

    Clozel MBreu VGray GAet al: Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J Pharmacol Exp Ther 270:2282351994Clozel M Breu V Gray GA et al: Pharmacological characterization of bosentan a new potent orally active nonpeptide endothelin receptor antagonist. J Pharmacol Exp Ther 270:228–235 1994

    • Search Google Scholar
    • Export Citation
  • 4.

    Clozel MGray GABreu Vet al: The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun 186:8678731992Clozel M Gray GA Breu V et al: The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun 186:867–873 1992

    • Search Google Scholar
    • Export Citation
  • 5.

    Clozel MWatanabe H: BQ-123, a peptidic endothelin ETA receptor antagonist, prevents the early cerebral vasospasm following subarachnoid hemorrhage after intracisternal but not intravenous injection. Life Sci 52:8258341993Clozel M Watanabe H: BQ-123 a peptidic endothelin ETA receptor antagonist prevents the early cerebral vasospasm following subarachnoid hemorrhage after intracisternal but not intravenous injection. Life Sci 52:825–834 1993

    • Search Google Scholar
    • Export Citation
  • 6.

    Cosentino FMcMahon EGCarter JSet al: Effect of endothelin A-receptor antagonist BQ-123 and phosphoramidon on cerebral vasospasm. J Cardiovasc Pharmacol 22 (Suppl 8):S332S3351993Cosentino F McMahon EG Carter JS et al: Effect of endothelin A-receptor antagonist BQ-123 and phosphoramidon on cerebral vasospasm. J Cardiovasc Pharmacol 22 (Suppl 8):S332–S335 1993

    • Search Google Scholar
    • Export Citation
  • 7.

    Doherty AMPatt WCEdmunds JJet al: Discovery of a novel series of orally active non-peptide endothelin-A (ETA) receptorselective antagonists. J Med Chem 38:125912631995Doherty AM Patt WC Edmunds JJ et al: Discovery of a novel series of orally active non-peptide endothelin-A (ETA) receptorselective antagonists. J Med Chem 38:1259–1263 1995

    • Search Google Scholar
    • Export Citation
  • 8.

    Feger GISchilling LEhrenreich Het al: Endothelin-induced contraction and relaxation of rat isolated basilar artery: effect of BQ-123. J Cereb Blood Flow Metab 14:8458521994Feger GI Schilling L Ehrenreich H et al: Endothelin-induced contraction and relaxation of rat isolated basilar artery: effect of BQ-123. J Cereb Blood Flow Metab 14:845–852 1994

    • Search Google Scholar
    • Export Citation
  • 9.

    Filep JGClozel MFournier Aet al: Characterization of receptors mediating vascular responses to endothelin-1 in the conscious rat. Br J Pharmacol 113:8458521994Filep JG Clozel M Fournier A et al: Characterization of receptors mediating vascular responses to endothelin-1 in the conscious rat. Br J Pharmacol 113:845–852 1994

    • Search Google Scholar
    • Export Citation
  • 10.

    Foley PLCaner HHKassell NFet al: Reversal of subarachnoid hemorrhage-induced vasoconstriction with an endothelin receptor antagonist. Neurosurgery 34:1081131994Foley PL Caner HH Kassell NF et al: Reversal of subarachnoid hemorrhage-induced vasoconstriction with an endothelin receptor antagonist. Neurosurgery 34:108–113 1994

    • Search Google Scholar
    • Export Citation
  • 11.

    Fujimori AYanagisawa MSaito Aet al: Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage. Lancet 336:6331990 (Letter)Fujimori A Yanagisawa M Saito A et al: Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage. Lancet 336:633 1990 (Letter)

    • Search Google Scholar
    • Export Citation
  • 12.

    Hamann GIsenberg EStrittmatter Met al: Absence of elevation of big endothelin in subarachnoid hemorrhage. Stroke 24:3833861993Hamann G Isenberg E Strittmatter M et al: Absence of elevation of big endothelin in subarachnoid hemorrhage. Stroke 24:383–386 1993

    • Search Google Scholar
    • Export Citation
  • 13.

    Hirose HIde KSasaki Tet al: The role of endothelin and nitric oxide in modulation of normal and spastic cerebral vascular tone in the dog. Eur J Pharmacol 277:77871995Hirose H Ide K Sasaki T et al: The role of endothelin and nitric oxide in modulation of normal and spastic cerebral vascular tone in the dog. Eur J Pharmacol 277:77–87 1995

    • Search Google Scholar
    • Export Citation
  • 14.

    Itoh SSasaki TAsai Aet al: Prevention of delayed vasospasm by an endothelin ETA receptor antagonist, BQ-123: change of ETA receptor mRNA expression in a canine subarachnoid hemorrhage model. J Neurosurg 81:7597641994Itoh S Sasaki T Asai A et al: Prevention of delayed vasospasm by an endothelin ETA receptor antagonist BQ-123: change of ETA receptor mRNA expression in a canine subarachnoid hemorrhage model. J Neurosurg 81:759–764 1994

    • Search Google Scholar
    • Export Citation
  • 15.

    Itoh SSasaki TIde Ket al: A novel endothelin ETA receptor antagonist, BQ-485, and its preventive effect on experimental cerebral vasospasm in dogs. Biochem Biophys Res Commun 195:9699751993Itoh S Sasaki T Ide K et al: A novel endothelin ETA receptor antagonist BQ-485 and its preventive effect on experimental cerebral vasospasm in dogs. Biochem Biophys Res Commun 195:969–975 1993

    • Search Google Scholar
    • Export Citation
  • 16.

    Kitazono THeistad DDFaraci FM: Dilatation of the basilar artery in response to selective activation of endothelin B receptors in vivo. J Pharmacol Exp Ther 273:161995Kitazono T Heistad DD Faraci FM: Dilatation of the basilar artery in response to selective activation of endothelin B receptors in vivo. J Pharmacol Exp Ther 273:1–6 1995

    • Search Google Scholar
    • Export Citation
  • 17.

    Kitazono THeistad DDFaraci FM: Enhanced responses of the basilar artery to activation of endothelin-B receptors in stroke-prone spontaneously hypertensive rats. Hypertension 25: 4904941995Kitazono T Heistad DD Faraci FM: Enhanced responses of the basilar artery to activation of endothelin-B receptors in stroke-prone spontaneously hypertensive rats. Hypertension 25: 490–494 1995

    • Search Google Scholar
    • Export Citation
  • 18.

    Masaoka MSuzuki RHirata Yet al: Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. Lancet 1:14021989 (Letter)Masaoka M Suzuki R Hirata Y et al: Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. Lancet 1:1402 1989 (Letter)

    • Search Google Scholar
    • Export Citation
  • 19.

    Matsumura YIkegawa RSuzuki Yet al: Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinal fluid. Life Sci 49:8418481991Matsumura Y Ikegawa R Suzuki Y et al: Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinal fluid. Life Sci 49:841–848 1991

    • Search Google Scholar
    • Export Citation
  • 20.

    Nirei HHamada KShoubo Met al: An endothelin ETA receptor antagonist, FR139317, ameliorates cerebral vasospasm in dogs. Life Sci 52:186918741993Nirei H Hamada K Shoubo M et al: An endothelin ETA receptor antagonist FR139317 ameliorates cerebral vasospasm in dogs. Life Sci 52:1869–1874 1993

    • Search Google Scholar
    • Export Citation
  • 21.

    Ohlstein EHBeck GR JrDouglas SAet al: Nonpeptide endothelin receptor antagonists. II. Pharmacological characterization of SB 209670. J Pharmacol Exp Ther 271:7627681994Ohlstein EH Beck GR Jr Douglas SA et al: Nonpeptide endothelin receptor antagonists. II. Pharmacological characterization of SB 209670. J Pharmacol Exp Ther 271:762–768 1994

    • Search Google Scholar
    • Export Citation
  • 22.

    Pickard JDMurray GDIllingworth Ret al: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid hemorrhage: British aneurysm nimodipine trial. Br Med J 298:6366421989Pickard JD Murray GD Illingworth R et al: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid hemorrhage: British aneurysm nimodipine trial. Br Med J 298:636–642 1989

    • Search Google Scholar
    • Export Citation
  • 23.

    Plane FGarland CJ: Differential effects of acetylcholine, nitric oxide and levcromakalim on smooth muscle membrane potential and tone in the rabbit basilar artery. Br J Pharmacol 110:6516561993Plane F Garland CJ: Differential effects of acetylcholine nitric oxide and levcromakalim on smooth muscle membrane potential and tone in the rabbit basilar artery. Br J Pharmacol 110:651–656 1993

    • Search Google Scholar
    • Export Citation
  • 24.

    Rand VEGarland CJ: Endothelium-dependent relaxation to acetylcholine in the rabbit basilar artery: importance of membrane hyperpolarization. Br J Pharmacol 106:1431501992Rand VE Garland CJ: Endothelium-dependent relaxation to acetylcholine in the rabbit basilar artery: importance of membrane hyperpolarization. Br J Pharmacol 106:143–150 1992

    • Search Google Scholar
    • Export Citation
  • 25.

    Roux SLöffler BMGray GAet al: The role of endothelin in experimental cerebral vasospasm. Neurosurgery 37:78851995Roux S Löffler BM Gray GA et al: The role of endothelin in experimental cerebral vasospasm. Neurosurgery 37:78–85 1995

    • Search Google Scholar
    • Export Citation
  • 26.

    Sasaki TKassell NFYamashita Met al: Barrier disruption in the major cerebral arteries following experimental subarachnoid hemorrhage. J Neurosurg 63:4334401985Sasaki T Kassell NF Yamashita M et al: Barrier disruption in the major cerebral arteries following experimental subarachnoid hemorrhage. J Neurosurg 63:433–440 1985

    • Search Google Scholar
    • Export Citation
  • 27.

    Schilling LFeger GIEhrenreich Het al: Endothelin-3-induced relaxation of isolated rat basilar artery is mediated by an endothelial ETB-type endothelin receptor. J Cereb Blood Flow Metab 5:6997051995Schilling L Feger GI Ehrenreich H et al: Endothelin-3-induced relaxation of isolated rat basilar artery is mediated by an endothelial ETB-type endothelin receptor. J Cereb Blood Flow Metab 5:699–705 1995

    • Search Google Scholar
    • Export Citation
  • 28.

    Seifert VLöffler BMZimmermann Met al: Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J Neurosurg 82:55621995Seifert V Löffler BM Zimmermann M et al: Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm delayed ischemic neurological deficits and volume of hematoma. J Neurosurg 82:55–62 1995

    • Search Google Scholar
    • Export Citation
  • 29.

    Seo BOemar BSSiebenmann Ret al: Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation 89:120312081994Seo B Oemar BS Siebenmann R et al: Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation 89:1203–1208 1994

    • Search Google Scholar
    • Export Citation
  • 30.

    Shigeno TClozel MSakai Set al: The effect of bosentan, a new potent endothelin receptor antagonist, on the pathogenesis of cerebral vasospasm. Neurosurgery 37:87911995Shigeno T Clozel M Sakai S et al: The effect of bosentan a new potent endothelin receptor antagonist on the pathogenesis of cerebral vasospasm. Neurosurgery 37:87–91 1995

    • Search Google Scholar
    • Export Citation
  • 31.

    Shigeno TMimi TYanagisawa Met al: Possible role of endothelin in the pathogenesis of cerebral vasospasm. J Cardiovasc Pharmacol 17 (Suppl 7):S480S4831991Shigeno T Mimi T Yanagisawa M et al: Possible role of endothelin in the pathogenesis of cerebral vasospasm. J Cardiovasc Pharmacol 17 (Suppl 7):S480–S483 1991

    • Search Google Scholar
    • Export Citation
  • 32.

    Suzuki HSato SSuzuki Yet al: Increased endothelin concentration in CSF from patients with subarachnoid hemorrhage. Acta Neurol Scand 81:5535541990Suzuki H Sato S Suzuki Y et al: Increased endothelin concentration in CSF from patients with subarachnoid hemorrhage. Acta Neurol Scand 81:553–554 1990

    • Search Google Scholar
    • Export Citation
  • 33.

    Suzuki RMasaoka HHirata Yet al: The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 77:961001992Suzuki R Masaoka H Hirata Y et al: The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 77:96–100 1992

    • Search Google Scholar
    • Export Citation
  • 34.

    Takase HMoreau PLüscher TF: Endothelin receptor subtypes in small arteries: studies with FR139317 and bosentan. Hypertension 25:7397431995Takase H Moreau P Lüscher TF: Endothelin receptor subtypes in small arteries: studies with FR139317 and bosentan. Hypertension 25:739–743 1995

    • Search Google Scholar
    • Export Citation
  • 35.

    Willette RNZhang HMitchell MPet al: Nonpeptide endothelin antagonist. Cerebrovascular characterization and effects on delayed cerebral vasospasm. Stroke 25:245024561994Willette RN Zhang H Mitchell MP et al: Nonpeptide endothelin antagonist. Cerebrovascular characterization and effects on delayed cerebral vasospasm. Stroke 25:2450–2456 1994

    • Search Google Scholar
    • Export Citation
  • 36.

    Yamaura ITani EMaeda Yet al: Endothelin-1 of canine basilar artery in vasospasm. J Neurosurg 76:991051992Yamaura I Tani E Maeda Y et al: Endothelin-1 of canine basilar artery in vasospasm. J Neurosurg 76:99–105 1992

    • Search Google Scholar
    • Export Citation
  • 37.

    Zuccarello MKassell NFSasaki Tet al: Barrier disruption in the major cerebral arteries after experimental subarachnoid hemorrhage in spontaneously hypertensive and normotensive rats. Neurosurgery 21:5155221987Zuccarello M Kassell NF Sasaki T et al: Barrier disruption in the major cerebral arteries after experimental subarachnoid hemorrhage in spontaneously hypertensive and normotensive rats. Neurosurgery 21:515–522 1987

    • Search Google Scholar
    • Export Citation
  • 38.

    Zuccarello MLewis AIRapoport RM: Endothelin ETA and ETB receptors in subarachnoid hemorrhage-induced cerebral vasospasm. Eur J Pharmacol 259:R121994Zuccarello M Lewis AI Rapoport RM: Endothelin ETA and ETB receptors in subarachnoid hemorrhage-induced cerebral vasospasm. Eur J Pharmacol 259:R1–2 1994

    • Search Google Scholar
    • Export Citation
  • 39.

    Zuccarello MRomano APassalaqua Met al: Decreased endothelium-dependent relaxation in subarachnoid hemorrhage-induced vasospasm: role of ET-1. Am J Physiol 269:H1009H10151995Zuccarello M Romano A Passalaqua M et al: Decreased endothelium-dependent relaxation in subarachnoid hemorrhage-induced vasospasm: role of ET-1. Am J Physiol 269:H1009–H1015 1995

    • Search Google Scholar
    • Export Citation
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 109 63 12
Full Text Views 65 1 0
PDF Downloads 85 3 0
EPUB Downloads 0 0 0
PubMed
Google Scholar