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.
Keywords
- Cerebral Blood Flow
- Middle Cerebral Artery Occlusion
- Focal Ischemia
- Cereb Blood Flow
- Microvascular Perfusion
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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
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
Boulanger C, Luscher T (1990) Release of endothelin from the porcine aorta; inhibition by endothelin-derived nitric oxide. J Clin Invest 85: 587–590
Dawson DA, Ruetzler CA, Carlos TM (1996) Polymorphonuclear leukocytes and microcirculatory perfusion in acute stroke in the SHR. Keio J Med 45: 248–253
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
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
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
Gobel U, Theilen H, Kuschinsky W (1990) Congruence of total and perfused capillary network in rat brains. Circ Res 66: 271–281
Hunley TE, Iwasaki S, Homma T, et al. (1995) Nitric oxide and endothelin in pathophysiological settings. Pediatr Nephrol 9: 235–244.
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
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
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
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
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
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
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
Rubanyi GM, Polokoff MA (1994) Endothelins: molecular biology, biochemistry, pharmacology, physiology and pathophysiology. Pharmacol Rev 46: 325–415
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
Spatz M, Yasuma Y, Strasser A, et al. (1996) Cerebral postischemic hypoperfusion is mediated by ETA receptors. Brain Res 726: 242–246
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
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
Theilen H, Schrock H, Kuschinsky W (1993) Capillary perfusion during incomplete forebrain ischemia and reperfusion in rat brain. Am J Physiol 265: H642 - H648
Willette RN, Sauermelch C, Ezekiel M, et al. (1990) Effect of endothelin on cortical microvascular perfusion in rats. Stroke 21: 451–458
Yanagisawa M, Kurihara H, Kimura S, et al. (1988) A novel potent vasoconstrictive peptide produced by endothelial cells. Nature 332: 411–415
Editor information
Editors and Affiliations
Rights 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