Abstract
The central role of Endothelin (ET) in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is supported by several investigations. These investigations provided, furthermore, that changes of the ET-receptor expression and function in the wall of the cerebral arteries are a considerable factor for the development of CVS. The biological activity of ET-1 is mediated by two receptor subtypes, named ET(A) and ET(B). Under physiological conditions the dominant vasocontractile effect of ET-1 is mediated by ET(A)-receptors on smooth muscle cells (SMC), which is attenuated by an ET(B)-receptor dependent release of nitric oxide (NO) from endothelial cells (EC). In the physiological cerebrovasculature ECs express exclusively ET(B)- and SMCs only ET(A)-receptors. In case of CVS an increased expression of the ET(B)-receptor could be detected in cerebral vessels. However, the loss of the vasodilative and the missing of a vasocontractile ET(B)-receptor mediated effect was demonstrated. Therefore, any ET(B)-receptor mediated vasoactivity seems to be lost in case of CVS and the biological impact of the increased expression remains unclear so far. The ET(A)-receptor expression seems to be not increased during the development of CVS. Therefore, the proven increase of the ET-dependent vasocontractility seems to be rather by the loss of the ET(B)-receptor mediated effect than by an increased ET(A)-receptor activity. In spite of the more significant changes of the ET(B)-receptor expression the pathophysiological effect of ET, namely the vasoconstriction, seems to be exclusively mediated by the ET(A)-receptor. Therefore, tailored approaches for the treatment of CVS remain to be ET(A)-receptor selective antagonists.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bederson JB, Connolly ES Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2009;40:994–1025.
Raabe A, Beck J, Berkefeld J, Deinsberger W, Meixensberger J, Schmiedek P, et al. [Recommendations for the management of patients with aneurysmal subarachnoid hemorrhage]. Zentralbl Neurochir. 2005;66:79–91.
Salom JB, Torregrosa G, Alborch E. Endothelins and the cerebral circulation. Cerebrovasc Brain Metab Rev. 1995;7:131–52.
Vatter H, Zimmermann M, Seifert V, Schilling L. Experimental approaches to evaluate endothelin-A receptor antagonists. Methods Find Exp Clin Pharmacol. 2004;26:277–86.
Zimmermann M, Seifert V. Endothelin and subarachnoid hemorrhage: an overview. Neurosurgery 1998;43:863–75.
Seifert V, Loffler BM, Zimmermann M, Roux S, Stolke D. Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J Neurosurg. 1995;82:55–62.
Chow M, Dumont AS, Kassell NF. Endothelin receptor antagonists and cerebral vasospasm: an update. Neurosurgery 2002;51:1333–41.
Macdonald RL, Kakarieka A, Mayer S, Pasqualin A, Ruefenacht D, Schmiedek P, et al. Prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage with clazosentan, an endothelin receptor antagonist. 2006.
Vajkoczy P, Meyer B, Weidauer S, Raabe A, Thome C, Ringel F, et al. Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: results of a randomized, double-blind, placebo-controlled, multicenter phase IIa study. J Neurosurg. 2005;103:9–17.
Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol. 1999;61:391–415.
Böhm F, Pernow J. The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovasc Res. 2007 Oct 1;76(1):8–18.
Schiffrin EL. Vascular endothelin in hypertension. Vascul Pharmacol. 2005;43:19–29.
Hino A, Tokuyama Y, Kobayashi M, Yano M, Weir B, Takeda J, et al. Increased expression of endothelin B receptor mRNA following subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab. 1996;16:688–97.
Roux S, Loffler BM, Gray GA, Sprecher U, Clozel M, Clozel JP. The role of endothelin in experimental cerebral vasospasm. Neurosurgery 1995;37:78–85.
Yamaura I, Tani E, Maeda Y, Minami N, Shindo H. Endothelin-1 of canine basilar artery in vasospasm. J Neurosurg. 1992;76:99–105.
Hirose H, Ide K, Sasaki T, Takahashi R, Kobayashi M, Ikemoto F, et al. The role of endothelin and nitric oxide in modulation of normal and spastic cerebral vascular tone in the dog. Eur J Pharmacol. 1995;277:77–87.
Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T, Ley KF, et al. Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 2003;53:123–33; discussion 133–125.
Rubanyi GM, Polokoff MA. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev. 1994;46:325–415.
Vatter H, Zimmermann M, Tesanovic V, Raabe A, Schilling L, Seifert V. Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: inhibitory effect on endothelin(A) receptor-mediated contraction. J Neurosurg. 2005;102:1101–7.
Vatter H, Zimmermann M, Tesanovic V, Raabe A, Seifert V, Schilling L. Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist shown to be clinically effective for the treatment of cerebral vasospasm. Part II: effect on endothelin(B) receptor-mediated relaxation. J Neurosurg. 2005;102:1108–14.
Hansen-Schwartz J, Hoel NL, Zhou M, Xu CB, Svendgaard NA, Edvinsson L. Subarachnoid hemorrhage enhances endothelin receptor expression and function in rat cerebral arteries. Neurosurgery 2003;52:1188–94.
Vatter H, Konczalla J, Weidauer S, Preibisch C, Zimmermann M, Raabe A, et al. Effect of delayed cerebral vasospasm on cerebrovascular endothelin A receptor expression and function. J Neurosurg. 2007;107:121–7.
Ansar S, Vikman P, Nielsen M, Edvinsson L. Cerebovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage. Am J Physiol Heart Circ Physiol. 2007;293:H3750–58.
Stanimirovic DB, Bertrand N, McCarron R, Uematsu S, Spatz M. Arachidonic acid release and permeability changes induced by endothelins in human cerebromicrovascular endothelium. Acta Neurochir Suppl (Wien). 1994;60:71–5.
Vatter H, Konczalla J, Weidauer S, Preibisch C, Raabe A, Zimmermann M, et al. Characterization of the endothelin-B receptor expression and vasomotor function during experimental cerebral vasospasm. Neurosurgery 2007;60:1100–8.
Konczalla J, Vatter H, Weidauer S, Raabe A, Seifert V. Alteration of the cerebrovascular function of endothelin B receptor after subarachnoidal hemorrhage in the rat. Exp Biol Med (Maywood). 2006;231:1064–8.
D’Orleans-Juste P, Labonte J, Bkaily G, Choufani S, Plante M, Honore JC. Function of the endothelin(B) receptor in cardiovascular physiology and pathophysiology. Pharmacol Ther. 2002;95:221–38.
Conflict of interest statement We declare that we have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer-Verlag/Wien
About this paper
Cite this paper
Vatter, H., Konczalla, J., Seifert, V. (2011). Endothelin Related Pathophysiology in Cerebral Vasospasm: What Happens to the Cerebral Vessels?. In: Feng, H., Mao, Y., Zhang, J.H. (eds) Early Brain Injury or Cerebral Vasospasm. Acta Neurochirurgica Supplements, vol 110/1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0353-1_31
Download citation
DOI: https://doi.org/10.1007/978-3-7091-0353-1_31
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-0352-4
Online ISBN: 978-3-7091-0353-1
eBook Packages: MedicineMedicine (R0)