Atrial natriuretic peptide: its putative role in modulating the choroid plexus-CSF system for intracranial pressure regulation

  • C. E. Johanson
  • J. E. Donahue
  • A. Spangenberger
  • E. G. Stopa
  • J. A. Duncan
  • H. S. Sharma
Part of the Acta Neurochirurgica Supplementum book series (NEUROCHIRURGICA, volume 96)


Evidence continues to build for the role of atrial natriuretic peptide (ANP) in reducing cerebrospinal fluid (CSF) formation rate, and thus, intracranial pressure. ANP binds to choroid plexus (CP) epithelial cells. This generates cGMP, which leads to altered ion transport and the slowing of CSF production. Binding sites for ANP in CP are plentiful and demonstrate plasticity in fluid imbalance disorders; however, specific ANP receptors in epithelial cells need confirmation. Using antibodies directed against NPR-A and NPR-B, we now demonstrate immunostaining not only in the choroidal epithelium (including cytoplasm), but also in the ependyma and some endothelial cells of cerebral microvessels in adult rats (Sprague-Dawley). The choroidal and ependymal cells stained almost universally, thus substantiating the initial autoradiographic binding studies with 125IANP. Because ANP titers in human CSF have previously been shown to increase proportionally to increments in ICP, we propose a compensatory ANP modulation of CP function to down-regulate ICP in hydrocephalus. Further evidence for this notion comes from the current finding of increased frequency of “dark” epithelial cells in CP of hydrocephalic (HTx) rats, which fits our earlier observation that the “dark” choroidal cells, associated with states of reduced CSF formation, are increased by elevated ANP in CSF. Altogether, ANP neuroendocrine-like regulation at CSF transport interfaces and blood-brain barrier impacts brain fluid homeostasis.


CSF homeostasis natriuretic peptide receptors hydrocephalus cGMP brain natriuretic peptide 


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  1. 1.
    Boassa D, Yool AJ (2005) Physiological roles of aquaporins in the choroid plexus. Curr Top Dev Bio 67: 181–206Google Scholar
  2. 2.
    Brown J, Zuo Z (1993) C-type natriuretic peptide and atrial natriuretic peptide receptors of rat brain. Am J Physiol 264: R513–R523PubMedGoogle Scholar
  3. 3.
    Burgess A, Segal MB (1970) Morphological changes associated with inhibition of fluid transport in the rabbit choroid plexus. J Physiol 208: 88P–91PPubMedGoogle Scholar
  4. 4.
    Carcenac C, Herbute S, Masseguin C, Mani-Ponset L, Maurel D, Briggs R, Guell A, Gabrion JB (1999) Hindlimb-suspension and spaceflight both alter cGMP levels in rat choroid plexus. J Gravit Physiol 6: 17–24PubMedGoogle Scholar
  5. 5.
    Chodobski A, Szmydynger-Chodobska J, Cooper E, McKinley MJ (1992) Atrial natriuretic peptide does not alter cerebrospinal fluid formation in sheep. Am J Physiol 262: R860–R864PubMedGoogle Scholar
  6. 6.
    D’Souza SP, Davis M, Baxter GF (2004) Autocrine and paracrine actions of natriuretic peptides in the heart. Pharmacol Ther 101: 113–129PubMedCrossRefGoogle Scholar
  7. 7.
    Ellis DZ, Nathanson JA, Sweadner KJ (2000) Carbachol inhibits Na(+)-K(+)-ATPase activity in choroid plexus via stimulation of the NO/cGMP pathway. Am J Physiol Cell Physiol 279: C1685–C1693PubMedGoogle Scholar
  8. 8.
    Grove KL, Goncalves J, Picard S, Thibault G, Deschepper CF (1997) Comparison of ANP binding and sensitivity in brains from hypertensive and normotensive rats. Am J Physiol 272: R1344–R1353PubMedGoogle Scholar
  9. 9.
    Hashimoto K, Kikuchi H, Ishikawa M. Yokoi K, Kimura M, Itokawa Y (1990) The effect of atrial natriuretic peptide on intracranial pressure in a congenital hydrocephalic model. No To Shinkei 42: 683–687 [in Japanese]PubMedGoogle Scholar
  10. 10.
    Herbute S, Oliver J, Davet J, Viso M. Ballard RW, Gharib C, Gabrion J (1994) ANP binding sites are increased in choroid plexus of SLS-1 rats after 9 days of spaceflight. Aviat Space Environ Med 65: 134–138PubMedGoogle Scholar
  11. 11.
    Hertz L, Chen Y, Spatz M (2000) Involvement of non-neuronal brain cells in AVP-mediated regulation of water space at the cellular, organ, and whole-body level. J Neurosci Res 62: 480–490PubMedCrossRefGoogle Scholar
  12. 12.
    Hise MA, Johanson CE (1978) Inhibition of cerebrospinal fluid flow by dibutyryl guanosine-3′-5′-cyclic monophosphoric acid. Fed Proceed 37: 514Google Scholar
  13. 13.
    Johanson C (2003) The choroid plexus-CSF nexus: gateway to the brain. In: Conn PM (ed) Neuroscience in medicine. Humana Press, Totowa, NJ, pp 165–195Google Scholar
  14. 14.
    Johanson CE, Sweeney SM, Parmelee JT, Epstein MH (1990) Cotransport of sodium and chloride by the adult mammalian choroid plexus. Am J Physiol 258: C211–C216PubMedGoogle Scholar
  15. 15.
    Johanson CE, Preston JE, Chodobski A, Stopa EG, Szmydynger-Chodobska J, McMillan PN (1999) AVP V1 receptor-mediated decrease in Cl-efflux and increase in dark cell number in choroid plexus epithelium. Am J Physiol 276: C82–C90PubMedGoogle Scholar
  16. 16.
    Johanson C, McMillan P, Tavares R, Spangenberger A, Duncan J, Silverberg G, Stopa E (2004) Homeostatic capabilities of the choroid plexus epithelium in Alzheimer’s disease. Cerebrospinal Fluid Res 1: 3PubMedCrossRefGoogle Scholar
  17. 17.
    Liszczak TM, Black PM, Foley L (1986) Arginine vasopressin causes morphological changes suggestive of fluid transport in rat choroid plexus epithelium. Cell Tissue Res 246: 379–385PubMedCrossRefGoogle Scholar
  18. 18.
    Nilsson C, Lindvall-Axelsson M, Owman C (1992) Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid system. Brain Res Brain Res Rev 17: 109–138PubMedCrossRefGoogle Scholar
  19. 19.
    Preston JE, McMillan PN, Stopa EG, Nashold JR, Duncan JA, Johanson CE (2003) Atrial natriuretic peptide induction of dark epithelial cells in choroid plexus: consistency with the model of CSF downregulation in hydrocephalus. Eur J Pediatr Surg 13: S40–S42PubMedCrossRefGoogle Scholar
  20. 20.
    Raichle ME (1981) Hypothesis: a central neuroendocrine system regulates brain ion homeostasis and volume. Adv Biochem Psychopharmacol 28: 329–336PubMedGoogle Scholar
  21. 21.
    Schalk KA, Faraci FM, Williams JL, VanOrden D, Heistad DD (1992) Effect of atriopeptin on production of cerebrospinal fluid. J Cereb Blood Flow Metab 12: 691–696PubMedGoogle Scholar
  22. 22.
    Silverberg GD, Huhn S, Jaffe RA, Chang SD, Saul T, Heit G, Von Essen A, Rubenstein E (2002) Downregulation of cerebro-Atrial natriuretic peptide: its putative role in modulating the choroid plexus-CSF system 455 spinal fluid production in patients with chronic hydrocephalus. J Neurosurg 97: 1271–1275PubMedCrossRefGoogle Scholar
  23. 23.
    Spector R, Johanson CE (1989) The mammalian choroid plexus. Sci Am 261: 68–74PubMedCrossRefGoogle Scholar
  24. 24.
    Steardo L, Nathanson JA (1987) Brain barrier tissues: end organs for atriopeptins. Science 235: 470–473PubMedGoogle Scholar
  25. 25.
    Tei S, Vagnetti D, Secca T, Santarella B, Roscani C, Farnesi RM (1995) Response of guanylate cyclase to atrial natriuretic factor in epithelial cells of the frog choroid plexus. Tissue Cell 27: 233–240PubMedCrossRefGoogle Scholar
  26. 26.
    Tulassay T, Khoor A, Bald M, Ritvay J, Szabo A, Rascher W (1990) Cerebrospinal fluid concentrations of atrial natriuretic peptide in children. Acta Paediatr Hung 30: 201–207PubMedGoogle Scholar
  27. 27.
    Vagnetti D, Tei S, Secca T, Santarella B, Roscani C, Farnesi RM (1995) Biochemical and cytochemical analyses of BNP-stimulated guanylate cyclase in frog choroid plexus. Brain Res 705: 295–301PubMedCrossRefGoogle Scholar
  28. 28.
    Weaver CE, McMillan PN, Duncan JA, Stopa EG, Johanson CE (2004) Hydrocephalus disorders: their biophysical and neuroendocrine impact on the choroid plexus epithelium. In: Hertz L (ed) Advances in molecular and cell biology. Elsevier Press, Greenwich, CT, pp 269–293Google Scholar
  29. 29.
    Welch K (1975) The principles of physiology of the cerebrospinal fluid in relation to hydrocephalus including normal pressure hydrocephalus. Adv Neurol 13: 247–332PubMedGoogle Scholar
  30. 30.
    Yamasaki H, Sugino M, Ohsawa N (1997) Possible regulation of intracranial pressure by human atrial natriuretic peptide in cerebrospinal fluid. Eur Neurol 38: 88–93PubMedGoogle Scholar
  31. 31.
    Zorad S, Alsasua A, Saavedra JM (1991) A modified quantitative autoradiographic assay for atrial natriuretic peptide receptors in rat brain. J Neurosci Methods 40: 63–69PubMedCrossRefGoogle Scholar
  32. 32.
    Zorad S, Alsasua A, Saavedra JM (1998) Decreased expression of natriuretic peptide A receptors and decreased cGMP production in the choroid plexus of spontaneously hypertensive rats. Mol Chem Neuropathol 33: 209–222PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • C. E. Johanson
    • 2
    • 1
  • J. E. Donahue
    • 3
  • A. Spangenberger
    • 2
  • E. G. Stopa
    • 2
    • 3
  • J. A. Duncan
    • 2
  • H. S. Sharma
    • 4
  1. 1.Department of NeurosurgeryRhode Island HospitalProvidenceUSA
  2. 2.Department of Clinical Neuroscience, Brown Medical SchoolRhode Island HospitalProvidenceUSA
  3. 3.Department of Pathology, Brown Medical SchoolRhode Island HospitalProvidenceUSA
  4. 4.Department of Surgical Sciences, Anesthesiology & Intensive Care MedicineUniversity HospitalUppsalaSweden

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