Cell and Tissue Research

, Volume 276, Issue 3, pp 559–564 | Cite as

Nitric oxide synthase in the rat carotid body and carotid sinus

  • Brigitte Höhler
  • Bernd Mayer
  • Wolfgang Kummer


The participation of nitric oxide synthase (NOS) in the innervation of the rat carotid body and carotid sinus was investigated by means of NADPH-diaphorase histochemistry and NOS immunohistochemistry using antisera raised against purified neuronal NOS and a synthetic tridecapeptide. NOS was detected in 23% of neurons at the periphery of the carotid bodies. Some negative neurons were surrounded by NOS-positive terminals. NOS-containing varicose nerve fibres innervated the arterial vascular bed and, to a lesser extent, the islands of glomus cells. These fibres persisted after transection of the carotid sinus nerve and are probably derived from intrinsic neurons. Large NOS-positive axonal swellings in the wall of the carotid sinus were absent after transection of the sinus nerve, indicating their sensory origin. The results suggest a neuronal nitrergic control of blood flow, neuronal activity and chemoreception in the carotid body, and an intrinsic role of NO in the process of arterial baroreception.

Key words

Baroreceptor Carotid body Carotid sinus Chemoreceptor Nitric oxide Nitric oxide synthase NADPH-diaphorase histochemistry Rat (Wistar) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acker H, O'Regan RG (1981) The effects of stimulation of autonomic nerves on carotid body blood flow in the cat. J Physiol (Lond) 315:99–110Google Scholar
  2. Aimi Y, Fujimura M, Vincent SR, Kimura H (1991) Localization of NADPH-diaphorase-containing neurons in sensory ganglia of the rat. J Comp Neurol 306:382–392Google Scholar
  3. Anderson CR (1992) NADPH diaphorase-positive neurons in the rat spinal cord include a subpopulation of autonomic preganglionic neurons. Neurosci Lett 139:280–284Google Scholar
  4. Blottner D, Baumgarten HG (1992) Nitric oxide synthetase (NOS)-containing sympathoadrenal cholinergic neurons of the rat IML-cell column: Evidence from histochemistry, immunohistochemistry, and retrograde labeling. J Comp Neurol 316:45–55Google Scholar
  5. Böck P, Gorgas K (1976) Fine structure of baroreceptor terminals in the carotid sinus of guinea pigs and mice. Cell Tissue Res 170:95–112Google Scholar
  6. Bredt DS, Hwang PM, Snyder SM (1990) Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347:768–770Google Scholar
  7. Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH (1991) Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351:714–718Google Scholar
  8. Briggs CA (1992) Potentiation of nicotinic transmission in the rat superior cervical sympathetic ganglion: effects of cyclic GMP and nitric oxide generators. Brain Res 573:139–146Google Scholar
  9. Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Vanmaercke YM, Herman AG (1990) Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 345:346–347Google Scholar
  10. Burnett AL, Lowenstein CJ, Bredt DS, Chang TSK, Snyder SH (1992) Nitric oxide: a physiologic mediator of penile erection. Science 257:401–403Google Scholar
  11. Daly M de Burgh, Lambertsen CJ, Schweitzer A (1954) Observations on the volume of blood flow and oxygen utilisation of the carotid body in the cat. J Physiol (Lond) 125:67–89Google Scholar
  12. Dawson TD, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991) Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801Google Scholar
  13. Desai KM, Sessa WC, Vane JR (1991) Involvement of nitric oxide in the reflex relaxation of the stomach to accomodate food or fluid. Nature 351:477–479Google Scholar
  14. Fischer A, Mundel P, Mayer B, Preissler U, Philippin B, Kummer W (1993) Nitric oxide synthase in guinea pig lower airway innervation Neurosci Lett 149:157–160Google Scholar
  15. Förstermann U, Schmidt HHHW, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F (1991) Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol 42:1849–1857Google Scholar
  16. Grozdanovic Z, Baumgarten HG, Brüning G (1992) Histochemistry of NADPH-diaphorase, a marker for neuronal nitric oxide synthase, in the peripheral autonomic nervous system of the mouse. Neuroscience 48:225–235Google Scholar
  17. Gustafsson LE, Wiklund CU, Wiklund NP, Persson MG, Moncada S (1990) Modulation of autonomic neuroeffector transmission by nitric oxide in guinea pig ileum. Biochem Biophys Res Commun 173:106–110Google Scholar
  18. Herdegen T, Brecht S, Mayer B, Leah J, Kummer W, Bravo R, Zimmermann M (1993) Long-lasting expression of JUN and KROX transcription factors and nitric oxide synthase in intrinsic neurons of the rat brain following axotomy. J Neurosci 13:4130–4145Google Scholar
  19. Hope BT, Michael GJ, Knigge KM, Vincent SR (1991) Neuronal NADPH diaphorase is a nitric oxide synthetase. Proc Natl Acad Sci USA 88:2811–2814Google Scholar
  20. Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD (1992) Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 267:14519–14522Google Scholar
  21. Klatt P, Heinzel B, John M, Kastner M, Böhme E, Mayer B (1992) Ca2+/calmodulin-dependent cytochrome c reductase activity of brain nitric oxide synthase. J Biol Chem 267:11374–11378Google Scholar
  22. Knoche H, Schmitt G (1964) Beitrag zur Kenntnis des Nervengewebes in der Wand des Sinus caroticus. I. Mitteilung. Z Zellforsch 63:22–36Google Scholar
  23. Knowles RG, Moncada S (1992) Nitric oxide as a signal in blood vessels. Trends Biol Sci 17:399–402Google Scholar
  24. Kummer W, Reinecke M, Heym C (1991) Neurotensin-like immunoreactivity in presumptive baroreceptor neurons innervating the guinea pig carotid sinus. J Auton Nerv Syst 35:107–116Google Scholar
  25. Kummer W, Fischer A, Mundel P, Mayer B, Hoba B, Philippin B, Preissler U (1992) Nitric oxide synthase in VIP-containing vasodilator nerve fibres in the guinea-pig. Neuroreport 3:653–655Google Scholar
  26. Li CG, Rand MJ (1990) Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus. Eur J Pharmacol 191:303–309Google Scholar
  27. McCloskey DI, Torrance RW (1971) Autoregulation of blood flow in the carotid body. Respir Physiol 13:23–35Google Scholar
  28. McDonald DM, Larue DT (1983) The ultrastructure and connections of blood vessels supplying the rat carotid body and carotid sinus. J Neurocytol 12:117–153Google Scholar
  29. McDonald DM, Mitchell RA (1975) The innervation of glomus cells, ganglion cells and blood vessels in the rat carotid body; a quantitative ultrastructural analysis. J Neurocytol 4:177–230Google Scholar
  30. McGehee DS, Goy MF, Oxford GS (1992) Involvement of the nitric oxide-cyclic GMP pathway in the desensitization of bradykinin responses of cultured rat sensory neurons. Neuron 9:315–324Google Scholar
  31. Morris R, Southam E, Braid DJ, Garthwaite J (1992) Nitric oxide may act as a messenger between dorsal root ganglion neurones and their satellite cells. Neurosci Lett 137:29–32Google Scholar
  32. O'Regan RG (1981) Responses of carotid body chemosensory activity and blood flow to stimulation of sympathetic nerves in the cat. J Physiol (Lond) 315:81–98Google Scholar
  33. Prabhakar NR, Kumar GK, Chang CH, Agani FH, Haxhiu MA (1993) Nitric oxide in the sensory function of the carotid body. Brain Res 625:16–22Google Scholar
  34. Rees PM (1967) Observations on the fine structure and distribution of presumptive baroreceptor nerves at the carotid sinus. J Comp Neurol 131:517–548Google Scholar
  35. Schmidt HHHW, Gagne GC, Nakane M, Pollock JS, Miller MF, Murad F (1992) Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanyly cyclase, and novel paraneural functions for nitrinergic signal transduction. J Histochem Cytochem 40:1439–1456Google Scholar
  36. Sheng H, Hughes ML, Murad F, Briggs CA (1992) Evidence that nitric oxide mediates the cyclic GMP response to synaptic activity in the rat superior cervical ganglion. Brain Res 597:343–345Google Scholar
  37. Snyder SH (1992) Nitric oxide and neurons. Curr Opin Neurobiol 2:323–327Google Scholar
  38. Thomas E, Pearse AGE (1961) The fine localization of dehydrogenases in the nervous system. Histochemie 2:266–282Google Scholar
  39. Toda N, Okamura T (1991) Role of nitric oxide in neurally induced cerebroarterial relaxation. J Pharmacol Exp Ther 258:1027–1032Google Scholar
  40. Vincent SR, Kimura H (1992) Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience 46:755–784Google Scholar
  41. Wang ZZ, Stensaas LJ, Dinger B, Fidone SJ (1989) Immunocytochemical localization of choline acetyltransferase in the carotid body of the cat and rabbit. Brain Res 498:131–134Google Scholar
  42. Wang ZZ, Stensaas LJ, Vente J de, Dinger B, Fidone SJ (1991) Immunocytochemical localization of cAMP and cGMP in cells of the rat carotid body following natural and pharmacological stimulation. Histochemistry 96:523–530Google Scholar
  43. Xie Q, Cho HJ, Calaycay J, Mumford RA, Swiderek KM, Lee TD, Ding A, Troso T, Nathan C (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Brigitte Höhler
    • 1
  • Bernd Mayer
    • 2
  • Wolfgang Kummer
    • 1
  1. 1.Institute for Anatomy and Cell BiologyPhilipps University MarburgMarburgGermany
  2. 2.Institute for Pharmacology and ToxicologyKarl Franzens UniversityGrazAustria

Personalised recommendations