Central Adrenergic Regulation of Cerebral Microvascular Permeability and Blood Flow; Anatomic and Physiologic Evidence

  • B. K. Hartman
  • L. W. Swanson
  • M. E. Raichle
  • S. H. Preskorn
  • H. B. Clark
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 131)


One of the early observations made using dopamine-β-hydroxylase (DBH) immunohistochemistry was a close association of centrally derived varicose adrenergic nerve fibers with small blood vessels, deep within the brain parenchyma (1,2). The central origin of these DBH-positive fibers was established by demonstrating their persistence after bilateral superior cervical ganglionectomy (3). On the basis of this anatomic association, it was hypothesized that one function of the central adrenergic system was regulation of the cerebral microvasculature (1–3). This association of central DBH-containing fibers with small blood vessels, including capillaries, was first demonstrated in rat brain, but subsequently has been demonstrated in the brain of superior cervical ganglionectomized monkeys (4) and human brain (3). A similar association had been observed using catecholamine histofluorescence (5) and a central origin also confirmed in ganglionectomized animals. The central innervation hypothesis has, however, been questioned because of a lack of physiologic and electron microscopic evidence (6).


Cerebral Blood Flow Vascular Permeability Locus Coeruleus Basal Lamina Capillary Permeability 
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  1. 1.
    Hartman BK, Udenfriend S: The application of immunological techniques to the study of enzymes regulating catecholamine synthesis and degradation. Pharmacol Rev 24: 311, 1972.PubMedGoogle Scholar
  2. 2.
    Hartman BK, Zide D, Udenfriend S: The use of dopamine-β-hydroxylase as a marker for the central noradrenergic nervous system in the rat brain. Proc Natl Acad Sci (USA) 69: 2722, 1972.CrossRefGoogle Scholar
  3. 3.
    Hartman BK: The innervation of cerebral blood vessels by central noradrenergic neurons. In, Usden E and Snyder SH (eds): Frontiers in Catecholamine Research, New York, Pergamon Press, 1973, pp 91–96.CrossRefGoogle Scholar
  4. 4.
    Raichle ME, Hartman BK, Eichling JO, et al: Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Natl Acad Sci (USA) 72: 37262–3720, 1975.CrossRefGoogle Scholar
  5. 5.
    Csillik B, Jancso G, Toth S, et al: Adrenergic innervation of hypothalamic blood vessels: A contribution to the problem of central thermodetectors. Acta Anat 80: 142–151, 1971.CrossRefPubMedGoogle Scholar
  6. 6.
    Edvinsson L, Lindvall O, Nielsen KC, et al: Are brain vessels innervated also by central (non-sympathetic) adrenergic neurons? Brain Res 63: 496–499, 1973.CrossRefPubMedGoogle Scholar
  7. 7.
    Rennels ML, Nelson E: Capillary innervation in the mammalian central nervous system: An electron microscopic demonstration.. Am J Anat 144: 233–241, 1975.CrossRefPubMedGoogle Scholar
  8. 8.
    Swanson LW, Connelly MA, Hartman BK: Ultrastructural evidence for central monoaminergic innervation of blood vessels of paraventricular nucleus of the hypothalamus. Brain Res 136: 166–173, 1977.CrossRefPubMedGoogle Scholar
  9. 9.
    Devine LE, Simpson FO: The fine structure of vascular sympathetic neuromuscular contacts in the rat. Am J Anat 121: 153–174, 1967.CrossRefPubMedGoogle Scholar
  10. 10.
    Verity MZ, Bevan JA: Fine structural study of the terminal effector plexus, neuromuscular and intermuscular relationships in the pulmonary artery. J Anat 103: 49, 1968.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Cervos-Novarro J, Matakas I: Electron microscopic evidence for innervation of intracerebral arterioles in the cat. Neurology 24: 282–286, 1974.CrossRefGoogle Scholar
  12. 12.
    Nelson E, Rennels M: Innervation of intracranial arteries. Brain 93: 475–490, 1970.CrossRefPubMedGoogle Scholar
  13. 13.
    Itakura T, Kazumi M, Tohyama M, et al: Central dual innervation of arterioles and capillaries in brain. Stroke 8: 360–365, 1977.CrossRefPubMedGoogle Scholar
  14. 14.
    Brightman MW, Klatzo I, Olsson Y, et al: The blood-brain barrier to proteins under normal and pathologic conditions. J Neurol Sci 10: 215–239, 1970.CrossRefPubMedGoogle Scholar
  15. 15.
    Herbst TJ, Raichle ME, Ferrendelli JA: β-adrenergic regulation of adenosine 3′,5′-monophosphate concentration in brain microvessels. Science 204: 330 - 332, 1979.CrossRefPubMedGoogle Scholar
  16. 16.
    Palmer GG: Beta adrenergic receptors mediate adenylate cyclase responses in rat cerebral capillaries. Neuropharmacology, in press.Google Scholar
  17. 17.
    Krogh A: The Anatomy and Physiology of Capillaries, New Haven, Yale University Press, 1929, pp 107–109.CrossRefGoogle Scholar
  18. 18.
    Farquhar MG, Hartman JF: Electron microscopy of cerebral capillaries. Anat Rec 124: 288, 1956.Google Scholar
  19. 19.
    Majno G, Shea SM, Leventhal M: Endothelial contraction induced by histamine-type mediators. J Cell Biol 42: 647–672, 1969.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Fillenz M: Innervation of pulmonary capillaries. Experientia (Basel) 25: 842, 1969.CrossRefGoogle Scholar
  21. 21.
    Raichle ME, Eichling JO, Straatmann MG, et al: Blood-brain barrier permeability of 11C-labeled alcohols and 150-labeled water. Am J Physiol 230: 543–552, 1976.PubMedGoogle Scholar
  22. 22.
    Eichling JO, Raichle ME, Grubb RL, et al: Evidence of the limitations of water as a freely diffusible tracer in brain of the Rhesus monkey. Circ Res 35: 358–364, 1974CrossRefPubMedGoogle Scholar
  23. 23.
    Renkin EM: Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscles. Am J Physiol 197: 1205–1210, 1959.PubMedGoogle Scholar
  24. 24.
    Crone C: Permeability of capillaries in various organs as determined by use of the indicator diffusion method. Acta Physiol Scand 58: 292–305, 1963.CrossRefPubMedGoogle Scholar
  25. 25.
    Raichle ME, Eichling JO, Grubb RL, et al: Central noradrenergic regulation of brain microcirculation. In, Hanna M, Pappius H., Feindel W: Dynamics of Brain Edema, New York, Springer-Verlag, 1976, pp 11–17.Google Scholar
  26. 26.
    Hartman BK, Swanson LW, Raichle ME, et al: Evidence for central adrenergic regulation of cerebral vascular permeability and blood flow. In, Usdin E (ed): Catecholamines: Basic and Clinical Frontiers, New York, Pergamon Press, 1978, 450–452.Google Scholar
  27. 27.
    Hartman BK: Immunofluorescence of dopamine-β-hydroxylase. Application of improved methodology to the localization of the peripheral and central noradrenergic nervous system. J Histochem Cytochem 21: 312–332, 1973.CrossRefPubMedGoogle Scholar
  28. 28.
    Shalit MN, Reinmuth OM, Shimojya S, et al: Carbon dioxide and cerebral circulatory control. 3. The effects of brain stem lesions. Arch Neurol 17: 342–347, 1967.CrossRefPubMedGoogle Scholar
  29. 29.
    Scheinberg P: Evidence for a brain stem center regulating CBF. Scand J Clin Invest (Suppl 102) 22:VIC, 1965.Google Scholar
  30. 30.
    Rosendorff C: The measurement of local cerebral blood flow and the effect of amines. Prog Brain Res 35: 115–156, 1972.CrossRefPubMedGoogle Scholar
  31. 31.
    Raichle ME, Grubb RL Jr, Eichling JO: Osmotically induced changes in brain water permeability. Fed Proc 36: 470, 1977.Google Scholar
  32. 32.
    Raichle ME, Grubb RL Jr: Acute arterial hypertension and brain water permeability. Fed Proc 37:242,. 1978.Google Scholar
  33. 33.
    Raichle ME, Grubb RL Jr: Regulation of brain water permeability by centrally-released vasopressin. Brain Res 143: 191–194, 1978.CrossRefPubMedGoogle Scholar
  34. 34.
    Swanson LW: Immunohistochemical evidence for a neurophysin-containing autonomic pathway arising in the paraventricular nucleus of the hypothalamus. Brain Res 128: 346–353, 1977.CrossRefPubMedGoogle Scholar
  35. 35.
    Dahlstrom A, Fuxe K: Evidence for the existence of mono-amine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand 62: 1–55 (Suppl 232), 1964.Google Scholar
  36. 36.
    Swanson LW, Hartman BK: The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-β-hydroxylase as a marker. J Comp Neurol 163: 467–505, 1975.CrossRefPubMedGoogle Scholar
  37. 37.
    Svensson TH, Thoren P: Brain noradrenergic neurons in the locus coeruleus: Inhibition by blood volume load through vagal afferents. Brain Res 172: 174–178, 1979.CrossRefPubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • B. K. Hartman
    • 1
    • 2
    • 3
    • 4
    • 5
  • L. W. Swanson
    • 1
    • 2
    • 3
    • 4
    • 5
  • M. E. Raichle
    • 1
    • 2
    • 3
    • 4
    • 5
  • S. H. Preskorn
    • 1
    • 2
    • 3
    • 4
    • 5
  • H. B. Clark
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Department of PsychiatryWashington University School of MedicineSt. LouisUSA
  2. 2.Department of NeurobiologyWashington University School of MedicineSt. LouisUSA
  3. 3.Department of AnatomyWashington University School of MedicineSt. LouisUSA
  4. 4.Department of NeurologyWashington University School of MedicineSt. LouisUSA
  5. 5.Department of Radiology-Division of Radiation SciencesWashington University School of MedicineSt. LouisUSA

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