Skip to main content

Effect of EndothelinA Receptor Antagonist on Neuronal Injury in Global and Focal Ischemia

  • Conference paper
Maturation Phenomenon in Cerebral Ischemia III

Summary

The involvement of endogenous endothelin-1 (ET-1) was evaluated in transient global brain ischemia (8 min) with reperfusion (72 h) and in focal permanent ischemia (4 h) of spontaneously hypertensive rats (SHR). In gerbils, postischemic treatment with an ETA receptor antagonist, Ro 61–1790, reversed the ischemia-induced hypoperfusion and preserved 64–74% of hippocampal CA1 neurons, compared with controls (20–44%). The pretreatment of SHR with Ro 61–1790 significantly increased cerebral microvascular perfusion, which was associated with a significant decrease (27%) in the volume of the ischemic lesion. These findings support the hypothesis that endogenously released ET-1 is an important mediator of ischemic injury.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barone FC, Globus MY-T, Price WJ, et al. (1994) Endothelin levels increase in rat and focal global ischemia. J Cereb Blood Flow Metab 14: 337–342

    Article  PubMed  CAS  Google Scholar 

  2. Sian L-G, Zhang T-X, Zhao WG, et al. (1994) Increased endothelin-1 in the rabbit model of middle cerebral artery occlusion. Neurosci Lett 174: 47–50

    Article  Google Scholar 

  3. Boulanger C, Luscher T (1990) Release of endothelin from the porcine aorta; inhibition by endothelin-derived nitric oxide. J Clin Invest 85: 587–590

    Article  PubMed  CAS  Google Scholar 

  4. Dawson DA, Ruetzler CA, Carlos TM (1996) Polymorphonuclear leukocytes and microcirculatory perfusion in acute stroke in the SHR. Keio J Med 45: 248–253

    Article  PubMed  CAS  Google Scholar 

  5. Dawson DA, Ruetzler CA, Hallenbeck JM (1997) Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat. Brain Res 749: 200–208

    Article  PubMed  CAS  Google Scholar 

  6. Ehrenreich H, Lange M, Near KA, et al. (1992) Long-term monitoring of immunoreactive endothelin-1 and endothelin-3 in ventricular cerebrospinal fluid, plasma, and 24 hr urine of patients with subarachnoid hemorrhage. Res Exp Med 192: 257–268

    Article  CAS  Google Scholar 

  7. Ehrenreich H, Schilling L (1995) New developments in the understanding of cerebral vasoregulatian and vasospasm: the endothelin-nitric oxide network. Cleveland J Med 62: 105–116

    CAS  Google Scholar 

  8. Gobel U, Theilen H, Kuschinsky W (1990) Congruence of total and perfused capillary network in rat brains. Circ Res 66: 271–281

    Article  PubMed  CAS  Google Scholar 

  9. Hunley TE, Iwasaki S, Homma T, et al. (1995) Nitric oxide and endothelin in pathophysiological settings. Pediatr Nephrol 9: 235–244.

    Article  PubMed  CAS  Google Scholar 

  10. Kaplan B, Brant S, Tanabe J, et al. (1991) Temporal thresholds for neocortical infarction in rats subjected to reversible focal ischemia. Stroke 22: 1032–1039

    Article  PubMed  CAS  Google Scholar 

  11. Kelly PAT, Edvinsson L, Ritchie IM (1995) The endothelin antagonist FR139317 attenuates the cerebrovascular effects of NG-nitro-L-arginine methyl ester in vivo. J Cereb Blood Flow Metab 15 [Suppl 1]: S458

    Google Scholar 

  12. Macrae IM, Robinson MJ, Graham DI, et al. (1993) Endothelin-1 induced reduction in cerebral blood flow: dose dependency, time course and neuropathological consequences. J Cereb Blood Flow Metab 13: 276–284

    Article  PubMed  CAS  Google Scholar 

  13. Osborne KA, Shigeno T, Balarsky AM, et al. (1987) Quantitative assessment of early brain damage in a rat model of focal cerebral ischaemia. J Neural Neurosurg Psychiatry 50: 402–410

    Article  CAS  Google Scholar 

  14. Panza JA, Quyyumi AA, Brush JE, Jr., et al. (1990) Abnormal endothelin-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323: 22–27

    Article  PubMed  CAS  Google Scholar 

  15. Patel TR, Galbraith S, Graham DI, et al. (1996) Endothelin receptor antagonist increases cerebral perfusion and reduces ischaemic damage in feline focal cerebral ischaemia. J Cereb Blood Flow Metab 16: 95–958

    Google Scholar 

  16. Roux S, Breu V, Gifler T, et al. (1997) Ro 61–1790, a new hydrosoluble endothelin antagonist: general pharmacology and effects on experimental cerebral vasospasm. J Pharmacol Exp Ther 283: 1110–1118

    PubMed  CAS  Google Scholar 

  17. Rubanyi GM, Polokoff MA (1994) Endothelins: molecular biology, biochemistry, pharmacology, physiology and pathophysiology. Pharmacol Rev 46: 325–415

    PubMed  CAS  Google Scholar 

  18. Spatz M, Stanimirovic D, Strasser A, et al. (1995) Nitra-L-arginine augments the endothelin-1 content of cerebrospinal fluid induced by cerebral ischemia. Brain Res 684: 99–103

    Article  PubMed  CAS  Google Scholar 

  19. Spatz M, Yasuma Y, Strasser A, et al. (1996) Cerebral postischemic hypoperfusion is mediated by ETA receptors. Brain Res 726: 242–246

    Article  PubMed  CAS  Google Scholar 

  20. Stasch J-P, Hirth-Dietrich C, Frobel K, et al. (1995) Prolonged endothelin blockade prevents hypertension and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats. Am J Hyperten 11: 1128–1134

    Article  Google Scholar 

  21. Suzuki R, Masaoka H, Hirata Y, et al. (1992) The role of endothelin-1 in the original of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 77: 96–100

    Article  PubMed  CAS  Google Scholar 

  22. Theilen H, Schrock H, Kuschinsky W (1993) Capillary perfusion during incomplete forebrain ischemia and reperfusion in rat brain. Am J Physiol 265: H642 - H648

    PubMed  CAS  Google Scholar 

  23. Willette RN, Sauermelch C, Ezekiel M, et al. (1990) Effect of endothelin on cortical microvascular perfusion in rats. Stroke 21: 451–458

    Article  PubMed  CAS  Google Scholar 

  24. Yanagisawa M, Kurihara H, Kimura S, et al. (1988) A novel potent vasoconstrictive peptide produced by endothelial cells. Nature 332: 411–415

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ohara, Y. et al. (1999). Effect of EndothelinA Receptor Antagonist on Neuronal Injury in Global and Focal Ischemia. In: Ito, U., Fieschi, C., Orzi, F., Kuroiwa, T., Klatzo, I. (eds) Maturation Phenomenon in Cerebral Ischemia III. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58602-6_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-58602-6_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-65023-2

  • Online ISBN: 978-3-642-58602-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics