Skip to main content
SpringerLink
Log in

Endothelin in the Middle Cerebral Artery: A Case of Multiple System Atrophy

  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Abstract

In this study, we show the changes in the wall of the middle cerebral artery of a subject who suffered multiple system atrophy with autonomic failure. An electron-immunocytochemical approach was employed to reveal the presence of endothelin-1. Our results demonstrate the presence of immunoreactive endothelin-1 in the endothelial cells of the intima, vascular smooth muscle cells and macrophages of the media and neointima, and perivascular nerves/axons varicosities at the adventitial-medial border of the artery. It is concluded that endothelin-1 may, therefore, play a number of roles within diseased cerebral artery. The finding of endothelin-1-positive varicosities of autonomic innervation to this artery suggests an influence of neural endothelin on vascular smooth muscle in multiple system atrophy with autonomic failure. However, the presence of features such as neointima formation, wall irregularities and foam cells suggest the coexistence of atherosclerosis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aliev G, Miah S, Turmaine M, Burnstock G(1995) An ultrastructural and immunocytochemical study of aortic endothelium in aged Sprague-Dawley rats. J Submicrosc Cytol Pathol 27: 477–490.

    Google Scholar 

  • Aliev G, Smith MA, Turmaine M, Neal ML, Zimina TV, Friedland RP, Perry G, LaManna JC, Burnstock G (2001) Atherosclerotic lesions are associated with increased immunoreactivity for inducible nitric oxide synthase and endothelin-1 in thoracic aortic intimal cells of hyperlipidemic Watanabe rabbits. Exp Mol Pathol 71: 40–54.

    Google Scholar 

  • Barger AC, Beeuwkes R 3rd, Lainey LL, Silverman KJ (1984) Hypothesis: Vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N Engl J Med 310: 175–177.

    Google Scholar 

  • Bevan R, Dodge J, Nichols P, Poseno T, Vijayakumaran E, Wellman T, Bevan JA (1998) Responsiveness of human infant cerebral arteries to sympathetic nerve stimulation and vasoactive agents. Pediatr Res 44: 730–739.

    Google Scholar 

  • Bevan JA, Dodge J, Walters CL, Wellman T, Bevan RD (1999) As human pial arteries (internal diameter 200–1000 μm) get smaller, their wall thickness and capacity to develop tension relative to their diameter increase. Life Sci 65: 1153–1161.

    Google Scholar 

  • Bredt DS, Hwang PM, Snyder SH (1990) Localization of nitric oxide synthase indicating a neuronal role for nitric oxide. Nature 347: 768–770.

    Google Scholar 

  • Brooks DJ, Redmond S, Mathias CJ, Bannister R, Symon L (1989) The effect of orthostatic hypotension on cerebral blood flow and middle cerebral artery velocity in autonomic failure, with observations on the action of ephedrine. J Neurol Neurosurg Psychiatry 52: 962–966.

    Google Scholar 

  • Damon DH (1998) Postganglionic sympathetic neurons express endothelin. Am J Physiol 274: R873–R878

    Google Scholar 

  • Damon DH (2001) NGF-independent survival of postganglionic sympathetic neurons in neuronal-vascular smooth muscle cocultures. Am J Physiol Heart Circ Physiol 280: H1722–H1728.

    Google Scholar 

  • De Aguilera EM, Irurzun A, Vila JM, Aldasoro M, Galeote MS, Lluch S (1990) Role of endothelium and calcium channels in endothelininduced contraction of human cerebral arteries. Br J Pharmacol 99: 439–440.

    Google Scholar 

  • De Marinis M, Stocchi F, Gregori B, Accornero N (2000) Sympathetic skin response and cardiovascular autonomic function tests in Parkinson's disease and multiple system atrophy with autonomic failure. Mov Disord 15: 1215–1220.

    Google Scholar 

  • Dhital KK, Gerli R, Lincoln J, Milner P, Tanganelli P, Weber G, Fruschelli C, Burnstock G (1988) Increased density of perivascular nerves to the major cerebral vessels of the spontaneously hypertensive rat: Differential changes in noradrenaline and neuropeptide Y during development. Brain Res 444: 33–45.

    Google Scholar 

  • Diedrich AU, Robertson DA (2002) Multiple system atrophy. eMedicine 3(1).

  • Edvinsson L, Ekman R, Jansen I, Ottosson A, Uddman R (1987) Peptidecontaining nerve fibers in human cerebral arteries: Immunocytochemistry, radioimmunoassay, and in vitro pharmacology. Ann Neurol 21: 431–437.

    Google Scholar 

  • Fernandez N, Monge L, Garcia JL, Garcia-Villalon AL, Gomez B, Dieguez G (1998) In vivo and in vitro action of endothelin-1 on goat cerebrovascular bed. Eur J Pharmacol 348: 199–211.

    Google Scholar 

  • Furchgott RF, Khan MT, Jothianandan D (1987) Evidence supporting the proposal that endothelium-derived relaxing factor is nitric oxide. Thromb Res (Suppl. VII), 5.

  • Goldie RG (1999) Endothelins in health and disease: An overview. Clin Exp Pharmacol Physiol 26: 145–148.

    Google Scholar 

  • Gorelova E, Loesch A, Bodin L, Chadwick L, Hamlyn PJ, Burnstock G (1996) Localization of immunoreactive Factor VIII, nitric oxide synthase, substance P, endothelin-1 and 5-hydroxytryptamine in human postmortem middle cerebral artery. J Anat 188: 97–107.

    Google Scholar 

  • Graham JG, Oppenheimer DR (1969) Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 32: 28–34.

    Google Scholar 

  • Horimoto Y, Aiba I, Yasuda T, Ohkawa Y, Katayama T, Yokokawa Y, Goto A, Ito Y (2000) Cerebral atrophy in multiple system atrophy by MRI. J Neurol Sci 173: 109–112.

    Google Scholar 

  • Ignarro LJ, Wood KS, Byrns RE (1986) Pharmacological and biological properties of EDRF: Evidence that EDRF is closely related to nitric oxide (NO) radical. Circulation 74 (Suppl. II): II–287.

    Google Scholar 

  • Komuro I, Kurihara H, Sugiyama T, Yoshizumi M, Takaku F, Yazaki Y (1988) Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett 238: 249–252.

    Google Scholar 

  • Lerman A, Edwards BS, Hallett JW, Heublein DM, Sandberg SM, Burnett JC (1991) Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med 325: 997–1001.

    Google Scholar 

  • Libby P (2002) Atherosclerosis: The new view. Sci Am May: 29–37.

  • Loesch A (2002) Perivascular nerves and vascular endothelium: Recent advances. Histol Histopathol 17: 591–597.

    Google Scholar 

  • Loesch A, Burnstock G (1996a) Immunocytochemistry of vasoactive agents and nitric oxide synthase in vascular endothelial cells with emphasis on the cerebral blood vessels. Cell Vision 3: 346–357.

    Google Scholar 

  • Loesch A, Burnstock G (1996b) Ultrastructural study of perivascular nerve fibres and endothelial cells of the rat basilar artery immunolabelled with monoclonal antibodies to neuronal and endothelial nitric oxide synthase. J Neurocytol 25: 525–534.

    Google Scholar 

  • Loesch A, Burnstock G (1998) Perivascular nerve fibres and endothelial cells of rat basilar artery: Immuno-gold labelling of antigenic sites for type I and type III nitric oxide synthase. J Neurocytol 27: 197–204.

    Google Scholar 

  • Loesch A, Burnstock G (2002) Endothelin in human cerebrovascular nerves. Clin Sci 103 (Suppl. 48): 404S–407S.

    Google Scholar 

  • Loesch A, Domer FR, Alexander B, Burnstock G (1993) Electronimmunocytochemistry of peptides in endothelial cells of rabbit cerebral vessels following perfusion with a perfluorocarbon emulsion. Brain Res 611: 333–337.

    Google Scholar 

  • Loesch A, Milner P, Burnstock G (1998) Endothelin in perivascular nerves. An electron-immunocytochemical study of rat basilar artery. NeuroReport 9: 3903–3906.

    Google Scholar 

  • Mathias CJ (1997) Autonomic disorders and their recognition. N Engl J Med 336: 721–724.

    Google Scholar 

  • Mathias CJ, Kimber JR (1999) Postural hypotension: Causes, clinical features, investigation, and management. Annu Rev Med 50: 317–336.

    Google Scholar 

  • Miller RC, Pelton JT, Huggins JP (1993) Endothelins: From receptors to medicine. TIPS 14: 54–60.

    Google Scholar 

  • Milner P, Loesch A, Burnstock G (2000a) Neural endothelin in hypertension: Increased immunoreactivity in ganglia and nerves to cerebral arteries of the spontaneously hypertensive rat. J Vasc Res 37: 39–49.

    Google Scholar 

  • Milner P, Loesch A, Burnstock G (2000b) Endothelin immunoreactivity and mRNA expression in sensory and sympathetic neurones following selective denervation. Int J Devl Neurosci 18: 722–734.

    Google Scholar 

  • Nabel EG, Yang ZY, Plautz G, Forough R, Zhan X, Haudenschild CC, Maciag T, Nabel GJ (1993) Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo. Nature 362: 844–846.

    Google Scholar 

  • Nozaki K, Moskowitz MA, Maynard KI, Koketsu N, Dawson TM, Bredt DS, Snyder SH (1993) Possible origins and distribution of immunoreactive nitric oxide synthase-containing nerve fibres in cerebral arteries. J Cereb Blood Flow Metab 13: 70–79.

    Google Scholar 

  • Ralevic V, Burnstock G (1995) Neuropeptides in blood pressure control. In: Laragh JH, Brenner BM eds. Hypertension: Pathophysiology, Diagnosis and Management, 2nd edn, New York: Raven Press Ltd, pp. 801–831.

    Google Scholar 

  • Rehman HU (2001) Multiple system atrophy. Postgrad Med J 77: 379–382.

    Google Scholar 

  • Robertson DA, Shannon JR, Jordan J, Davis TL, Diedrich A, Jacob G, Garland E, Tellioglu T, Biaggioni I (2001) Multiple system atrophy: Newdevelopments in pathophysiology and therapy. Parkinsonism Relat Disord 7: 257–260.

    Google Scholar 

  • Salani D, Taraboletti G, Rosano L, Di Castro V, Borsotti P, Giavazzi R, Bagnato A (2000) Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Am J Pathol 157: 1703–1711.

    Google Scholar 

  • Sharifi AM, Schiffrin EL (1997) Apoptosis in aorta of deoxycorticosterone acetate-salt hypertensive rats: Effect of endothelin receptor antagonism. J Hypertens 15: 1441–1448.

    Google Scholar 

  • Shochina M, Loesch A, Rubino A, Miah S, Macdonald G, Burnstock G (1997) Immunoreactivity for nitric oxide synthase and endothelin in the coronary and basilar arteries of renal hypertensive rats. Cell Tissue Res 288: 509–516.

    Google Scholar 

  • Spokes EG, Bannister R, Oppenheimer DR (1979) Multiple system atrophy with autonomic failure: Clinical, histological and neurochemical observations on four cases. J Neurol Sci 43: 59–82.

    Google Scholar 

  • Toda N, Okamura T (1990) Possible role of nitric oxide in transmitting information from vasodilator nerve to cerebroarterial muscle. Biochem Biophys Res Commun 170: 308–313.

    Google Scholar 

  • Vanhoutte PM (2000) Say NO to ET. J Auton Nerv Syst 81: 271–277.

    Google Scholar 

  • Yanagisawa M, Kurihara K, Kimura S, Tomabe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelia cells. Nature 332: 411–415.

    Google Scholar 

  • Zimmermann M, Seifert V (1998) Endothelin and subarachnoid hemorrhage: An overview. Neurosurgery 43: 863–876.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK

    Isla Mickey & Andrzej Loesch

  2. University College London, Wakefield Street, London, WC1N 1PJ, UK

    Linda Kilford & Ann Kingsbury

Authors
  1. Isla Mickey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linda Kilford
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ann Kingsbury
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrzej Loesch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mickey, I., Kilford, L., Kingsbury, A. et al. Endothelin in the Middle Cerebral Artery: A Case of Multiple System Atrophy. Histochem J 34, 469–477 (2002). https://doi.org/10.1023/A:1024758504647

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1024758504647

Keywords

Search

Navigation