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Erschienen in: Acta Neurochirurgica 11/2011

01.11.2011 | Experimental Research

RETRACTED ARTICLE: Magnesium lithospermate B alleviates the production of endothelin-1 through an NO-dependent mechanism and reduces experimental vasospasm in rats

verfasst von: Chih-Zen Chang, Shu-Chuan Wu, Aij-Lie Kwan, Shi-Lin Hwang, Shen-Long Howng

Erschienen in: Acta Neurochirurgica | Ausgabe 11/2011

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Abstract

Objective

Magnesium lithospermate B (MLB), a working extract from Salvia miltiorrhiza, was effective against coronary artery disease, ischemic stroke, and chronic renal disease. This study examined the effect of MLB on endothelin-1/endothelial nitric oxide synthase (eNOS) in a subarachnoid hemorrhage (SAH) animal model.

Methods

A rodent double-hemorrhage model was employed. Animals were randomly assigned to five groups (sham, SAH only, vehicle, 10 mg/kg/day MLB treatment, and pretreatment groups). A radiolabeled NOS Assay Kit was used to detect eNOS. Serum and cerebrospinal fluid sampling for ET-1 (ELISA) was measured. The basilar arteries (BAs) were garnered and sliced, and their cross-sectional areas were determined. In addition, NOS inhibitor nitro-arginine methyl ester (L-NAME) was employed in the SAH+ MLB treatment groups.

Results

Significant vasoconstriction was perceived in the SAH group (lumen patency: 44.6%, p < 0.01), but not in the MLB group (lumen patency: 89.3%). The ET-1 level was reduced in the MLP plus SAH group (34%, p < 0.01) when compared with the SAH groups (SAH only and vehicle). MLB dose-dependently increased the level of eNOS when compared with the vehicle plus SAH group. However, the administration of L-NAME reversed the expression of eNOS and vasoconstriction (lumen patency: 56.2%) in the MLB group.

Conclusion

The enhanced expression of eNOS and decreased ET-1 levels in the MLB groups may reflect its anti-spastic effect. In the study of NOS, L-NAME reversed MLB’s anti-vasospastic effect. This finding lends credence to the hypothesis that MLB modulates ET-1 levels through a NOS-dependent mechanism in the pathogenesis of cerebral vasospasm following SAH.
Literatur
1.
Zurück zum Zitat Adams JD, Wang R, Yang J, Lien EJ (2006) Preclinical and clinical examinations of salvia miltiorrhiza and its tanshinones in ischemic conditions. Chin Med 1:3CrossRefPubMedPubMedCentral Adams JD, Wang R, Yang J, Lien EJ (2006) Preclinical and clinical examinations of salvia miltiorrhiza and its tanshinones in ischemic conditions. Chin Med 1:3CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Arrick DM, Mayhan WG (2010) Inhibition of endothelin-1 receptors improves impaired nitric oxide synthase-dependent dilation of cerebral arterioles in type-1 diabetic rats. Microcirculation 17(6):439–446PubMedPubMedCentral Arrick DM, Mayhan WG (2010) Inhibition of endothelin-1 receptors improves impaired nitric oxide synthase-dependent dilation of cerebral arterioles in type-1 diabetic rats. Microcirculation 17(6):439–446PubMedPubMedCentral
3.
Zurück zum Zitat Barone FC, Ohlstein EH, Hunter AJ, Campbell CA, Hadingham SH, Parsons AA, Yang Y, Shohami E (2000) Selective antagonism of endothelin-A-receptors improves outcome in both head trauma and focal stroke in rat. J Cardiovasc Pharmacol 36:S357–S361CrossRefPubMed Barone FC, Ohlstein EH, Hunter AJ, Campbell CA, Hadingham SH, Parsons AA, Yang Y, Shohami E (2000) Selective antagonism of endothelin-A-receptors improves outcome in both head trauma and focal stroke in rat. J Cardiovasc Pharmacol 36:S357–S361CrossRefPubMed
4.
Zurück zum Zitat Chan K, Chui SH, Wong DY, Ha WY, Chan CL, Wong RN (2004) Protective effects of danshensu from the aqueous extract of salvia miltiorrhiza (danshen) against homocysteine-induced endothelial dysfunction. Life Sci 75:3157–3171CrossRefPubMed Chan K, Chui SH, Wong DY, Ha WY, Chan CL, Wong RN (2004) Protective effects of danshensu from the aqueous extract of salvia miltiorrhiza (danshen) against homocysteine-induced endothelial dysfunction. Life Sci 75:3157–3171CrossRefPubMed
5.
Zurück zum Zitat Chang CZ, Wu SC, Kwan AL, Lin CL, Hwang SL (2011) 6-Mercaptopurine reverses experimental vasospasm and alleviates the production of endothelins in NO-independent mechanism-a laboratory study. Acta Neurochir (Wien) 153(4):939–949CrossRefPubMed Chang CZ, Wu SC, Kwan AL, Lin CL, Hwang SL (2011) 6-Mercaptopurine reverses experimental vasospasm and alleviates the production of endothelins in NO-independent mechanism-a laboratory study. Acta Neurochir (Wien) 153(4):939–949CrossRefPubMed
6.
Zurück zum Zitat Chang CZ, Yen CP, Winadi D, Wu SC, Howng SL, Lin TK, Jeng AY, Kassell NF, Kwan AL (2002) Attenuation of hemolysate-induced cerebrovascular endothelial cell injury and of production of endothelin-1 and big endothelin-1 by an endothelin-converting enzyme inhibitor. Surg Neurol 58(3–4):181–188CrossRefPubMed Chang CZ, Yen CP, Winadi D, Wu SC, Howng SL, Lin TK, Jeng AY, Kassell NF, Kwan AL (2002) Attenuation of hemolysate-induced cerebrovascular endothelial cell injury and of production of endothelin-1 and big endothelin-1 by an endothelin-converting enzyme inhibitor. Surg Neurol 58(3–4):181–188CrossRefPubMed
7.
Zurück zum Zitat Czóbel M, Kaszaki J, Molnár G, Nagy S, Boros M (2009) Nonspecific inhibition of nitric oxide synthesis evokes endothelin-dependent increases in myocardial contractility. Nitric Oxide 21(3–4):201–209CrossRefPubMed Czóbel M, Kaszaki J, Molnár G, Nagy S, Boros M (2009) Nonspecific inhibition of nitric oxide synthesis evokes endothelin-dependent increases in myocardial contractility. Nitric Oxide 21(3–4):201–209CrossRefPubMed
8.
Zurück zum Zitat Grasso G (2004) An overview of new pharmacological treatments for cerebrovascular dysfunction after experimental subarachnoid hemorrhage. Brain Res Brain Res Rev 44:49–63CrossRefPubMed Grasso G (2004) An overview of new pharmacological treatments for cerebrovascular dysfunction after experimental subarachnoid hemorrhage. Brain Res Brain Res Rev 44:49–63CrossRefPubMed
9.
Zurück zum Zitat Han JY, Fan JY, Horie Y, Miura S, Cui DH, Ishii H, Hibi T, Tsuneki H, Kimura I (2008) Ameliorating effects of compounds derived from salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion. Pharmacol Ther 117(2):280–295CrossRefPubMed Han JY, Fan JY, Horie Y, Miura S, Cui DH, Ishii H, Hibi T, Tsuneki H, Kimura I (2008) Ameliorating effects of compounds derived from salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion. Pharmacol Ther 117(2):280–295CrossRefPubMed
10.
Zurück zum Zitat Hansen-Schwartz J, Vajkoczy P, Macdonald RL, Pluta RM, Zhang JH (2007) Cerebral vasospasm: looking beyond vasoconstriction. Trends Pharmacol Sci 28:252–256CrossRefPubMed Hansen-Schwartz J, Vajkoczy P, Macdonald RL, Pluta RM, Zhang JH (2007) Cerebral vasospasm: looking beyond vasoconstriction. Trends Pharmacol Sci 28:252–256CrossRefPubMed
11.
Zurück zum Zitat Herrera M, Hong NJ, Ortiz PA, Garvin JL (2009) Endothelin-1 inhibits thick ascending limb transport via Akt-stimulated nitric oxide production. J Biol Chem 284(3):1454–1460CrossRefPubMedPubMedCentral Herrera M, Hong NJ, Ortiz PA, Garvin JL (2009) Endothelin-1 inhibits thick ascending limb transport via Akt-stimulated nitric oxide production. J Biol Chem 284(3):1454–1460CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Hsieh TC, Wu JM (2006) Differential control of growth, cell cycle progression, and gene expression in human estrogen receptor positive mcf-7 breast cancer cells by extracts derived from polysaccharopeptide i'm-yunity and danshen and their combination. Int J Oncol 29:1215–1222PubMed Hsieh TC, Wu JM (2006) Differential control of growth, cell cycle progression, and gene expression in human estrogen receptor positive mcf-7 breast cancer cells by extracts derived from polysaccharopeptide i'm-yunity and danshen and their combination. Int J Oncol 29:1215–1222PubMed
13.
Zurück zum Zitat Jeng AY, Mulder P, Kwan AL, Battistini B (2002) Nonpeptidic endothelin-converting enzyme inhibitors and their potential therapeutic applications. Can J Physiol Pharmacol 80(5):440–449CrossRefPubMed Jeng AY, Mulder P, Kwan AL, Battistini B (2002) Nonpeptidic endothelin-converting enzyme inhibitors and their potential therapeutic applications. Can J Physiol Pharmacol 80(5):440–449CrossRefPubMed
14.
Zurück zum Zitat Kang DG, Oh H, Chung HT, Lee HS (2003) Inhibition of angiotensin converting enzyme by lithospermic acid b isolated from radix salviae miltiorrhiza bunge. Phytother Res 17:917–920CrossRefPubMed Kang DG, Oh H, Chung HT, Lee HS (2003) Inhibition of angiotensin converting enzyme by lithospermic acid b isolated from radix salviae miltiorrhiza bunge. Phytother Res 17:917–920CrossRefPubMed
15.
Zurück zum Zitat Kästner S, Oertel MF, Scharbrodt W, Krause M, Böker DK, Deinsberger W (2005) Endothelin-1 in plasma, cisternal CSF and microdialysate following aneurysmal SAH. Acta Neurochir (Wien) 147(12):1271–1279CrossRefPubMed Kästner S, Oertel MF, Scharbrodt W, Krause M, Böker DK, Deinsberger W (2005) Endothelin-1 in plasma, cisternal CSF and microdialysate following aneurysmal SAH. Acta Neurochir (Wien) 147(12):1271–1279CrossRefPubMed
16.
Zurück zum Zitat 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):2–5CrossRef 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):2–5CrossRef
18.
Zurück zum Zitat Maier B, Lehnert M, Laurer HL, Marzi I (2007) Biphasic elevation in cerebrospinal fluid and plasma concentrations of endothelin 1 after traumatic brain injury in human patients. Shock 27:610–614CrossRefPubMed Maier B, Lehnert M, Laurer HL, Marzi I (2007) Biphasic elevation in cerebrospinal fluid and plasma concentrations of endothelin 1 after traumatic brain injury in human patients. Shock 27:610–614CrossRefPubMed
19.
Zurück zum Zitat Mitsutomi N, Akashi C, Odagiri J, Matsumura Y (1999) Effects of endogenous and exogenous nitric oxide on endothelin-1 production in cultured vascular endothelial cells. Eur J Pharmacol 364(1):65–73CrossRefPubMed Mitsutomi N, Akashi C, Odagiri J, Matsumura Y (1999) Effects of endogenous and exogenous nitric oxide on endothelin-1 production in cultured vascular endothelial cells. Eur J Pharmacol 364(1):65–73CrossRefPubMed
20.
Zurück zum Zitat Mori K, Yamamoto T, Miyazaki M, Hara Y, Aiko Y, Koike N, Sakamoto S, Nakao Y, Esaki T (2010) Optimal cerebrospinal fluid magnesium ion concentration for vasodilatory effect and duration after intracisternal injection of magnesium sulfate solution in a canine subarachnoid hemorrhage model. J Neurosurg 114(4):1–8 Mori K, Yamamoto T, Miyazaki M, Hara Y, Aiko Y, Koike N, Sakamoto S, Nakao Y, Esaki T (2010) Optimal cerebrospinal fluid magnesium ion concentration for vasodilatory effect and duration after intracisternal injection of magnesium sulfate solution in a canine subarachnoid hemorrhage model. J Neurosurg 114(4):1–8
21.
Zurück zum Zitat Ohkita M, Sugii M, Ka Y, Kitamura A, Mori T, Hayashi T, Takaoka M, Matsumura Y (2006) Differential effects of different statins on endothelin-1 gene expression and endothelial NOS phosphorylation in porcine aortic endothelial cells. Exp Biol Med (Maywood) 231(6):772–776PubMed Ohkita M, Sugii M, Ka Y, Kitamura A, Mori T, Hayashi T, Takaoka M, Matsumura Y (2006) Differential effects of different statins on endothelin-1 gene expression and endothelial NOS phosphorylation in porcine aortic endothelial cells. Exp Biol Med (Maywood) 231(6):772–776PubMed
22.
Zurück zum Zitat Ryttlefors M, Enblad P, Ronne-Engström E, Persson L, Ilodigwe D, Macdonald RL (2010) Patient age and vasospasm after subarachnoid hemorrhage. Neurosurgery 67(4):911–917CrossRefPubMed Ryttlefors M, Enblad P, Ronne-Engström E, Persson L, Ilodigwe D, Macdonald RL (2010) Patient age and vasospasm after subarachnoid hemorrhage. Neurosurgery 67(4):911–917CrossRefPubMed
23.
Zurück zum Zitat Sercombe R, Dinh YR, Gomis P (2002) Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol 88:227–249CrossRefPubMed Sercombe R, Dinh YR, Gomis P (2002) Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol 88:227–249CrossRefPubMed
24.
Zurück zum Zitat Turner JD, Mammis A, Prestigiacomo CJ (2010) Erythropoietin for the treatment of subarachnoid hemorrhage: a review. World Neurosurg 73(5):500–507CrossRefPubMed Turner JD, Mammis A, Prestigiacomo CJ (2010) Erythropoietin for the treatment of subarachnoid hemorrhage: a review. World Neurosurg 73(5):500–507CrossRefPubMed
25.
Zurück zum Zitat Tzen JT, Jinn TR, Chen YC, Li FY, Cheng FC, Shi LS, She HKh, Chen BC, Hsieh V, Tu ML (2007) Magnesium lithospermate B possesses inhibitory activity on Na+, K+−ATPase and neuroprotective effects against ischemic stroke. Acta Pharmacol Sin 28(5):609–615CrossRefPubMed Tzen JT, Jinn TR, Chen YC, Li FY, Cheng FC, Shi LS, She HKh, Chen BC, Hsieh V, Tu ML (2007) Magnesium lithospermate B possesses inhibitory activity on Na+, K+−ATPase and neuroprotective effects against ischemic stroke. Acta Pharmacol Sin 28(5):609–615CrossRefPubMed
26.
Zurück zum Zitat Vellimana AK, Milner E, Azad TD, Harries MD, Zhou ML, Gidday JM, Han BH, Zipfel GJ (2011) Endothelial nitric oxide synthase mediates endogenous protection against subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 42(3):776–782CrossRefPubMed Vellimana AK, Milner E, Azad TD, Harries MD, Zhou ML, Gidday JM, Han BH, Zipfel GJ (2011) Endothelial nitric oxide synthase mediates endogenous protection against subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 42(3):776–782CrossRefPubMed
27.
Zurück zum Zitat Wang C, Zhao X, Mao S, Wang Y, Cui X, Pu Y (2006) Management of SAH with traditional Chinese medicine in China. Neurol Res 28(4):436–444CrossRefPubMed Wang C, Zhao X, Mao S, Wang Y, Cui X, Pu Y (2006) Management of SAH with traditional Chinese medicine in China. Neurol Res 28(4):436–444CrossRefPubMed
28.
Zurück zum Zitat Wong GK, Boet R, Poon WS, Chan MT, Gin T, Ng SC, Zee BC (2011) Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care 15(1):R52CrossRefPubMedPubMedCentral Wong GK, Boet R, Poon WS, Chan MT, Gin T, Ng SC, Zee BC (2011) Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care 15(1):R52CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Yamamoto T, Esaki T, Nakao Y, Mori K (2010) Efficacy of low-dose tissue-plasminogen activator intracisternal administration for the prevention of cerebral vasospasm after subarachnoid hemorrhage. World Neurosurg 73(6):675–682CrossRefPubMed Yamamoto T, Esaki T, Nakao Y, Mori K (2010) Efficacy of low-dose tissue-plasminogen activator intracisternal administration for the prevention of cerebral vasospasm after subarachnoid hemorrhage. World Neurosurg 73(6):675–682CrossRefPubMed
30.
Zurück zum Zitat Yamashiro K, Milsom AB, Duchene J, Panayiotou C, Urabe T, Hattori N, Ahluwalia A (2010) Alterations in nitric oxide and endothelin-1 bioactivity underlie cerebrovascular dysfunction in ApoE-deficient mice. J Cereb Blood Flow Metab 30(8):1494–1503CrossRefPubMedPubMedCentral Yamashiro K, Milsom AB, Duchene J, Panayiotou C, Urabe T, Hattori N, Ahluwalia A (2010) Alterations in nitric oxide and endothelin-1 bioactivity underlie cerebrovascular dysfunction in ApoE-deficient mice. J Cereb Blood Flow Metab 30(8):1494–1503CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Yuen CY, Wong WT, Tian XY, Wong SL, Lau CW, Yu J, Tomlinson B, Yao X, Huang Y (2011) Telmisartan inhibits vasoconstriction via PPAR{gamma}-dependent expression and activation of endothelial nitric oxide synthase. Cardiovasc Res 90(1):122–129CrossRefPubMed Yuen CY, Wong WT, Tian XY, Wong SL, Lau CW, Yu J, Tomlinson B, Yao X, Huang Y (2011) Telmisartan inhibits vasoconstriction via PPAR{gamma}-dependent expression and activation of endothelial nitric oxide synthase. Cardiovasc Res 90(1):122–129CrossRefPubMed
32.
Zurück zum Zitat Zhang Y, Clark JF, Pyne-Geithman G, Caruso J (2010) Metallomics study in CSF for putative biomarkers to predict cerebral vasospasm. Metallomics 2(9):628–637CrossRefPubMed Zhang Y, Clark JF, Pyne-Geithman G, Caruso J (2010) Metallomics study in CSF for putative biomarkers to predict cerebral vasospasm. Metallomics 2(9):628–637CrossRefPubMed
33.
Zurück zum Zitat Zhou Z, Wang SQ, Liu Y, Miao AD (2006) Cryptotanshinone inhibits endothelin-1 expression and stimulates nitric oxide production in human vascular endothelial cells. Biochim Biophys Acta 1760:1–9CrossRefPubMed Zhou Z, Wang SQ, Liu Y, Miao AD (2006) Cryptotanshinone inhibits endothelin-1 expression and stimulates nitric oxide production in human vascular endothelial cells. Biochim Biophys Acta 1760:1–9CrossRefPubMed
Metadaten
Titel
RETRACTED ARTICLE: Magnesium lithospermate B alleviates the production of endothelin-1 through an NO-dependent mechanism and reduces experimental vasospasm in rats
verfasst von
Chih-Zen Chang
Shu-Chuan Wu
Aij-Lie Kwan
Shi-Lin Hwang
Shen-Long Howng
Publikationsdatum
01.11.2011
Verlag
Springer Vienna
Erschienen in
Acta Neurochirurgica / Ausgabe 11/2011
Print ISSN: 0001-6268
Elektronische ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-011-1082-6

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