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Acta Neurochirurgica

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01-07-2009 | Experimental Research

Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits

Authors: Volker Neuschmelting, Serge Marbacher, Ali-Reza Fathi, Stephan M. Jakob, Javier Fandino

Published in: Acta Neurochirurgica | Issue 7/2009

Abstract

Background

The role of endothelin-1 (ET-1) and nitric oxide (NO) as two important mediators in the development of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is controversial. The objective of this study was to determine whether local levels of ET-1 and NO in cerebral arterial plasma and/or in cerebrospinal fluid (CSF) are associated with the occurrence of CVS after SAH.

Methods

CVS was induced using the one-haemorrhage rabbit model and confirmed by digital subtraction angiography of the rabbits’ basilar artery on day 5. Prior to sacrifice, local CSF and basilar arterial plasma samples were obtained by a transclival approach to the basilar artery. Systemic arterial plasma samples were obtained. ET-1 levels were determined by immunometric technique (pg/ml ± SEM) and total nitrate/nitrite level spectrophotometrically (µmol/l ± SEM).

Findings

Angiographic CVS was documented after SAH induction (n = 12, P < 0.05). The ET-1 level in CSF was significantly elevated by 27.3% to 0.84 ± 0.08 pg/ml in SAH animals (n = 7) in comparison to controls (0.66 ± 0.04 pg/ml, n = 7, P < 0.05). There was no significant difference in ET-1 levels in systemic and basilar arterial plasma samples of SAH animals compared to controls. A significant lack of local NO metabolites was documented in basilar arterial plasma after SAH (36.8 ± 3.1 µmol/l, n = 6) compared to controls (61.8 ± 6.2 µmol/l, n = 6, P < 0.01).

Conclusion

This study demonstrates that an elevated ET-1 level in CSF and local lack of NO in the basilar arterial plasma samples are associated with CVS after experimental SAH.

Alabadi JA, Torregrosa G, Miranda FJ, Salom JB, Centeno JM, Alborch E (1997) Impairment of the modulatory role of nitric oxide on the endothelin-1-elicited contraction of cerebral arteries: a pathogenetic factor in cerebral vasospasm after subarachnoid hemorrhage. Neurosurgery 41:245–252 discussion 252-243PubMedCrossRef

Andresen J, Shafi NI, Bryan RM Jr (2006) Endothelial influences on cerebrovascular tone. J Appl Physiol 100:318–327PubMedCrossRef

Barth M, Capelle HH, Munch E, Thome C, Fiedler F, Schmiedek P, Vajkoczy P (2007) Effects of the selective endothelin A (ET(A)) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subarachnoid hemorrhage—preliminary results from a randomized clinical series. Acta Neurochir (Wien) 149:911–918 discussion 918CrossRef

Clark JF, Sharp FR (2006) Bilirubin oxidation products (BOXes) and their role in cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab 26:1223–1233PubMedCrossRef

Hanggi D, Steiger HJ (2006) Nitric oxide in subarachnoid haemorrhage and its therapeutics implications. Acta Neurochir (Wien) 148:605–613 discussion 613CrossRef

Hino A, Tokuyama Y, Weir B, Takeda J, Yano H, Bell GI, Macdonald RL (1996) Changes in endothelial nitric oxide synthase mRNA during vasospasm after subarachnoid hemorrhage in monkeys. Neurosurgery 39:562–567 discussion 567–568PubMedCrossRef

Iuliano BA, Pluta RM, Jung C, Oldfield EH (2004) Endothelial dysfunction in a primate model of cerebral vasospasm. J Neurosurg 100:287–294PubMedCrossRef

Jung CS, Iuliano BA, Harvey-White J, Espey MG, Oldfield EH, Pluta RM (2004) Association between cerebrospinal fluid levels of asymmetric dimethyl-L-arginine, an endogenous inhibitor of endothelial nitric oxide synthase, and cerebral vasospasm in a primate model of subarachnoid hemorrhage. J Neurosurg 101:836–842PubMedCrossRef

Juvela S (2000) Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage. J Neurosurg 92:390–400PubMedCrossRef

10.

Juvela S (2002) Plasma endothelin and big endothelin concentrations and serum endothelin-converting enzyme activity following aneurysmal subarachnoid hemorrhage. J Neurosurg 97:1287–1293PubMedCrossRef

11.

Kastner S, Oertel MF, Scharbrodt W, Krause M, Boker DK, Deinsberger W (2005) Endothelin-1 in plasma, cisternal CSF and microdialysate following aneurysmal SAH. Acta Neurochir (Wien) 147:1271–1279 discussion 1279CrossRef

12.

Kessler IM, Pacheco YG, Lozzi SP, de Araujo AS Jr, Onishi FJ, de Mello PA (2005) Endothelin-1 levels in plasma and cerebrospinal fluid of patients with cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Surg Neurol 64(Suppl 1):S1:2–5

13.

Levin ER (1995) Endothelins. N Engl J Med 333:356–363PubMedCrossRef

14.

Mascia L, Fedorko L, Stewart DJ, Mohamed F, terBrugge K, Ranieri VM, Wallace MC (2001) Temporal relationship between endothelin-1 concentrations and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. Stroke 32:1185–1190PubMed

15.

Menon DK, Day D, Kuc RE, Downie AJ, Chatfield DA, Davenport AP (2002) Arteriojugular endothelin-1 gradients in aneurysmal subarachnoid haemorrhage. Clin Sci (Lond) 103(Suppl 48):399S–403S

16.

Mima T, Yanagisawa M, Shigeno T, Saito A, Goto K, Takakura K, Masaki T (1989) Endothelin acts in feline and canine cerebral arteries from the adventitial side. Stroke 20:1553–1556PubMed

17.

Ng WH, Moochhala S, Yeo TT, Ong PL, Ng PY (2001) Nitric oxide and subarachnoid hemorrhage: elevated level in cerebrospinal fluid and their implications. Neurosurgery 49:622–626 discussion 626–627PubMedCrossRef

18.

Oechslin E, Kiowski W, Schindler R, Bernheim A, Julius B, Brunner-La Rocca HP (2005) Systemic endothelial dysfunction in adults with cyanotic congenital heart disease. Circulation 112:1106–1112PubMedCrossRef

19.

Ohkita M, Takaoka M, Shiota Y, Nojiri R, Matsumura Y (2002) Nitric oxide inhibits endothelin-1 production through the suppression of nuclear factor kappa B. Clin Sci (Lond) 103(Suppl 48):68S–71S

20.

Park KW, Metais C, Dai HB, Comunale ME, Sellke FW (2001) Microvascular endothelial dysfunction and its mechanism in a rat model of subarachnoid hemorrhage. Anesth Analg 92:990–996PubMedCrossRef

21.

Pluta RM (2005) Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment. Pharmacol Ther 105:23–56PubMedCrossRef

22.

Pluta RM, Boock RJ, Afshar JK, Clouse K, Bacic M, Ehrenreich H, Oldfield EH (1997) Source and cause of endothelin-1 release into cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg 87:287–293PubMedCrossRef

23.

Pluta RM, Thompson BG, Dawson TM, Snyder SH, Boock RJ, Oldfield EH (1996) Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm. J Neurosurg 84:648–654PubMedCrossRef

24.

Ridnour LA, Sim JE, Hayward MA, Wink DA, Martin SM, Buettner GR, Spitz DR (2000) A spectrophotometric method for the direct detection and quantitation of nitric oxide, nitrite, and nitrate in cell culture media. Anal Biochem 281:223–229PubMedCrossRef

25.

Sadamitsu D, Kuroda Y, Nagamitsu T, Tsuruta R, Inoue T, Ueda T, Nakashima K, Ito H, Maekawa T (2001) Cerebrospinal fluid and plasma concentrations of nitric oxide metabolites in postoperative patients with subarachnoid hemorrhage. Crit Care Med 29:77–79PubMedCrossRef

26.

Sakowitz OW, Wolfrum S, Sarrafzadeh AS, Stover JF, Dreier JP, Dendorfer A, Benndorf G, Lanksch WR, Unterberg AW (2001) Relation of cerebral energy metabolism and extracellular nitrite and nitrate concentrations in patients after aneurysmal subarachnoid hemorrhage. J Cereb Blood Flow Metab 21:1067–1076PubMedCrossRef

27.

Seifert V, Loffler BM, Zimmermann M, Roux S, Stolke D (1995) Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J Neurosurg 82:55–62PubMedCrossRef

28.

Suzuki H, Sato S, Suzuki Y, Takekoshi K, Ishihara N, Shimoda S (1990) Increased endothelin concentration in CSF from patients with subarachnoid hemorrhage. Acta Neurol Scand 81:553–554PubMedCrossRef

29.

Suzuki M, Asahara H, Endo S, Inada K, Doi M, Kuroda K, Ogawa A (1999) Increased levels of nitrite/nitrate in the cerebrospinal fluid of patients with subarachnoid hemorrhage. Neurosurg Rev 22:96–98PubMedCrossRef

30.

Suzuki R, Masaoka H, Hirata Y, Marumo F, Isotani E, Hirakawa K (1992) The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 77:96–100PubMedCrossRef

31.

Vajkoczy P, Meyer B, Weidauer S, Raabe A, Thome C, Ringel F, Breu V, Schmiedek P (2005) 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 103:9–17PubMedCrossRef

32.

Vatter H, Konczalla J, Weidauer S, Preibisch C, Zimmermann M, Raabe A, Seifert V (2007) Effect of delayed cerebral vasospasm on cerebrovascular endothelin A receptor expression and function. J Neurosurg 107:121–127PubMedCrossRef

33.

Vatter H, Weidauer S, Dias S, Preibisch C, Ngone S, Raabe A, Zimmermann M, Seifert V (2007) Persistence of the nitric oxide-dependent vasodilator pathway of cerebral vessels after experimental subarachnoid hemorrhage. Neurosurgery 60:179–187 discussion 187-178PubMed

34.

Woszczyk A, Deinsberger W, Boker DK (2003) Nitric oxide metabolites in cisternal CSF correlate with cerebral vasospasm in patients with a subarachnoid haemorrhage. Acta Neurochir (Wien) 145:257–263 discussion 263-254CrossRef

35.

Zimmermann M, Seifert V (1998) Endothelin and subarachnoid hemorrhage: an overview. Neurosurgery 43:863–875 discussion 875-866PubMedCrossRef

Title: Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits
Authors: Volker Neuschmelting
Serge Marbacher
Ali-Reza Fathi
Stephan M. Jakob
Javier Fandino
Publication date: 01-07-2009
Publisher: Springer Vienna
Published in: Acta Neurochirurgica / Issue 7/2009
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI: https://doi.org/10.1007/s00701-009-0350-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits

Abstract

Background

Methods

Findings

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Findings

Conclusion

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