Neural Transmitters and Central Mechanisms in Primary Hypertension

  • P. I. Korner
  • E. Badoer
  • G. A. Head
Conference paper

Abstract

Much of our current knowledge about the operation of the autonomic nervous system is based on input-output analysis of the mechanisms through which particular disturbances evoke distinctive autonomic response patterns. Most of this work has been based on analysing the responses to stimuli of relatively short duration, of only minutes and hours. However, our focus on circulatory regulation shifts to a longer time frame when considering the pathogenesis of hypertension, or the mechanisms of action of centrally acting antihypertensive drugs. Some of the latter are particularly valuable for probing molecular mechanisms, such as the neurotransmitters and membrane receptors, of cardiovascular neurons.

Keywords

Attenuation Dopamine Tyrosine Serotonin Angiotensin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Badoer E, Head GA, Korner PI (1983) Effects of intracisternal and intravenous a-methyldopa and clonidine on haemodynamics and baroreceptor-heart rate reflex properties in conscious rabbits. J Cardiovasc Pharmacol 5: 760–767PubMedCrossRefGoogle Scholar
  2. 2.
    Blessing WW, Chalmers JP (1979) Direct projection of catecholamine (presumably dopamine)- containing neurons from hypothalamus to spinal cord. Neurosci Lett 11: 35–40PubMedCrossRefGoogle Scholar
  3. 3.
    Blessing WW, Reis DJ (1982) Inhibitory cardiovascular function of neurons in the caudal ventro-lateral medulla of the rabbit: relationship to the area containing Al noradrenergic cells. Brain Res 253: 161–171PubMedCrossRefGoogle Scholar
  4. 4.
    Blessing WW, Chalmers JP, Howe PRC (1978) Distribution of catecholamine-containing cell bodies in the rabbit central nervous system. J Comp Neurol 179: 407–423PubMedCrossRefGoogle Scholar
  5. 5.
    Blombery PA, Korner PI (1979) Relative contributions of aortic and carotid sinus baroreceptors to the baroreceptor-heart rate reflex of the conscious rabbit. I Auton Nerv Syst 1: 161–171CrossRefGoogle Scholar
  6. 6.
    Chalmers JP (1975) Brain amines and models of experimental hypertension. Circ Res 36:469– 480Google Scholar
  7. 7.
    Chalmers JP, Reid JL (1972) Participation of central noradrenergic neurons in arterial baro- receptor reflexes in the rabbit: a study with intracisternally administered 6-hydroxydopamine. Circ Res 31: 789–804PubMedGoogle Scholar
  8. 8.
    Chalmers JP, West MJ (1983) The nervous system in the pathogenesis of essential hypertension. In: Robertson JIS (ed) Clinical aspects of essential hypertension. Elsevier, Amsterdam, pp 64–96 (Handbook of hypertension, vol 1 )Google Scholar
  9. 9.
    Chalmers JP, Wurtman RJ (1971) The fate of intracisternally administered norepinephrine-3H in the brain and spinal cord of the rabbit. J Pharmacol Exp Ther 178: 8–19PubMedGoogle Scholar
  10. 10.
    Dahlstrom A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand [Suppl 232] 62: 1–55Google Scholar
  11. 11.
    Dampney RAL, Goodchild AK, Robertson LG, Montgomery W (1982) Role of ventrolateral medulla in vasomotor regulation: a correlative anatomical and physiological study. Brain Res 249: 223–235PubMedCrossRefGoogle Scholar
  12. 12.
    Esler MD, Jackman G, Bobik A, Leonard P, Kelleher D, Skews H, Jennings G, Korner P (1981) Norepinephrine kinetics in essential hypertension; defective neuronal uptake of norepinephrine in some patients. Hypertension 3: 149–156PubMedGoogle Scholar
  13. 13.
    Esler MD, Hasking GJ, Willett IR, Leonard PW, Jennings GL (1985) Noradrenaline release and sympathetic nervous system activity. J Hypertens 3: 117–129PubMedCrossRefGoogle Scholar
  14. 13a.
    Evans MH (1980) Vasoactive sites in the diencephalon of the rabbit. Brain Res 183: 329–340PubMedCrossRefGoogle Scholar
  15. 14.
    Finch L, Haeusler G (1973) Further evidence for a central hypotensive action of a-methyldopa in both the rat and cat. Br J Pharmacol 47: 217–228PubMedGoogle Scholar
  16. 15.
    Folkow B (1982) Physiological aspects of primary hypertension. Physiol Rev 62: 347–504PubMedGoogle Scholar
  17. 16.
    Haeusler B (1971) Early pre- and postjunctional effects of 6-hydroxy dopamine. J Pharmacol Exp Ther 178: 49–62PubMedGoogle Scholar
  18. 17.
    Head GA, De Jong W (to be published) Differential blood pressure responses to intracisternal clonidine, a-methyldopa and 6-hydroxy dopamine in conscious normotensive and spontaneously hypertensive rats: involvement of a central pressor pathway. J Cardiovasc Pharmacol. In pressGoogle Scholar
  19. 18.
    Head GA, Korner PI (1980) Mechanisms of acute hypertension and bradycardia following intracisternal 6–hydroxydopamine in conscious rabbits. Eur J Pharmacol 66: 111–115PubMedCrossRefGoogle Scholar
  20. 19.
    Head GA, Korner PI (1982) Cardiovascular functions of brain serotonergic neurons in the rabbit as analysed from the acute and chronic effects of 5,6-dihydroxytryptamine. J Cardiovasc Pharmacol 4: 398–408PubMedCrossRefGoogle Scholar
  21. 20.
    Head GA, Korner PI, Lewis SL, Badoer E (1983) Contribution of noradrenergic and serotoner-gic neurons to the circulatory effects of centrally acting clonidine and a-methyldopa in rabbits. J Cardiovasc Pharmacol 5: 945–953PubMedCrossRefGoogle Scholar
  22. 21.
    Howe PRC, Lovenberg W, Chalmers JP (1981) Increased number of PNMT-immunofluorescent nerve cell bodies in the medulla oblongata of stroke-prone hypertensive rats. Brain Res 205: 123–130PubMedCrossRefGoogle Scholar
  23. 22.
    Jennings G, Korner P, Esler M, Restall R (1984) Redevelopment of essential hypertension after cessation of long–term therapy; preliminary findings. Clin Exp Hypertens [A] 6: 493–505CrossRefGoogle Scholar
  24. 23.
    Jonsson G, Sachs C (1970) Effects of 6-hydroxydopamine on the uptake and storage of norad-renaline in sympathetic adrenergic neurons. Eur J Pharmacol 9: 141–155PubMedCrossRefGoogle Scholar
  25. 24.
    Korner PI (1971) Integrative neural cardiovascular control. Physiol Rev 51: 312–367PubMedGoogle Scholar
  26. 25.
    Korner PI (1979) Central nervous control of autonomic cardiovascular function. In: Berne RM (ed) The heart. American Physiological Society, Bethesda, pp 691–739 (Handbook of physiology, Sect 2: The cardiovascular system, vol 1 )Google Scholar
  27. 26.
    Korner PI (1982) Causal and homeostatic factors in hypertension (Sixth Volhard Lecture). Clin Sci [Suppl 8] 63: 5s–26sGoogle Scholar
  28. 27.
    Korner PI (1983) The role of the heart in hypertension. In: Robertson JIS (ed) Clinical aspects of essential hypertension. Elsevier, Amsterdam, pp 97–132 (Handbook of hypertension, vol 1 ).Google Scholar
  29. 28.
    Korner PI, Angus JA (1981) Central nervous control of blood pressure in relation to antihyper-tensive drug treatment. Pharmacol Ther 13: 321–356PubMedCrossRefGoogle Scholar
  30. 29.
    Korner PI, Head GA (1981) Effects of noradrenergic and serotonergic neurons on blood pressure, heart rate and baroreceptor-heart rate reflex of the conscious rabbit. J Auton Nerv Syst 3: 511–523PubMedCrossRefGoogle Scholar
  31. 30.
    Korner PI, Shaw J, West MJ, Oliver JR (1972) Central nervous system control of baroreceptor reflexes in the rabbit. Circ Res 31: 637–652PubMedGoogle Scholar
  32. 31.
    Korner PI, Oliver JR, Sleight P, Chalmers JP, Robinson JS (1974) Effects of clonidine on the baroreceptor–heart rate reflex and on single aortic baroreceptor fibre discharge. Eur J Pharmacol 28: 189–198PubMedCrossRefGoogle Scholar
  33. 32.
    Korner PI, Oliver JR, Reynoldson JA, Head GA, Carson VJ, Walker MMcD (1978) Cardiovascular and behavioral effects of intracisternal 6-hydroxydopamine in the rabbit. Eur J Pharmacol 53: 83–93PubMedCrossRefGoogle Scholar
  34. 33.
    Korner PI, Reynoldson JA, Head GA, Oliver JR, Carson V (1979) Effect of 6-hydroxyl- dopamine on baroreceptor-heart rate and nasopharyngeal reflexes of the rabbit. J Cardiovasc Pharmacol 1: 311–328PubMedCrossRefGoogle Scholar
  35. 34.
    Korner PI, Head GA, Bobik A, Badoer E, Aberdeen JA (1984) Central and peripheral autonomic mechanisms involved in the circulatory actions of methyldopa. Hypertension [Suppl 2] 6:11–63–11–70Google Scholar
  36. 35.
    Korner PI, Head GA, Badoer E (1984) Effects of sinoaortic denervation on the acute circulatory responses to centrally administered 6-hydroxydopamine and of clonidine in conscious rabbits. J Cardiovasc Pharmacol 6: 909–913PubMedCrossRefGoogle Scholar
  37. 36.
    Korner PI, Jennings GL, Esler MD, Broughton A (1985) Role of cardiac and vascular amplifiers in the maintenance of hypertension and the effect of reversal of cardiovascular hypertrophy. Clin Exp Pharmacol Physiol 12: 205–209PubMedCrossRefGoogle Scholar
  38. 37.
    Kuhn DM, Wolf WA, Lovenberg W (1980) Review of the role of the central serotonergic neuronal system in blood pressure regulation. Hypertension 2: 243–255PubMedGoogle Scholar
  39. 38.
    Loewy AD, McKellar S (1980) The neuroanatomical basis of central cardiovascular control. Fed Proc 39: 2495–2503PubMedGoogle Scholar
  40. 39.
    Ostman–Smith I (1981) Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci 61: 265–272PubMedGoogle Scholar
  41. 40.
    Pickel VM, Joh TH, Reis DJ (1977) A serotonergic innervation of noradrenergic neurons in nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase. Brain Res 131: 197–214PubMedCrossRefGoogle Scholar
  42. 41.
    Reis DJ, Ross RA, Joh TH (1974) Some aspects of the reaction of central and peripheral nor–adrenergic neurons to injury. In: Fuxe K, Olsen L, Zotterman Y (eds) Dynamics of degeneration and growth in neurons. Pergamon, Oxford, pp 109–125Google Scholar
  43. 42.
    Reis DJ, Granata AR, Joh TH, Ross CA, Ruggiero DA, Park DH (1984) Brain stem catecholamine mechanisms in tonic and reflex control of blood pressure. Hypertension [Suppl 2] 6:11–7–11–15Google Scholar
  44. 43.
    Ross CA, Ruggiero DA, Joh TH, Park DH, Reis DJ (1983) Adrenaline synthesizing neurons in the rostral ventrolateral medulla: a possible role in tonic vasomotor control. Brain Res 273:356– 361Google Scholar
  45. 44.
    Ryall RW (1967) Effect of monoamines upon sympathetic preganglionic neurons.. Circ Res [Suppl 3] 20/21: III–83–III–87Google Scholar
  46. 45.
    Saavedra JM, Grobecker H, Axelrod J (1976) Adrenaline–forming enzyme in brainstem: elevation in genetic and experimental hypertension. Science 191:4 83–84CrossRefGoogle Scholar
  47. 46.
    Sherrington CS (1906) The integrative action of the nervous system. Yale University Press, New HavenGoogle Scholar
  48. 47.
    Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand [Suppl] 367: 1–48Google Scholar
  49. 48.
    Wing LMH, Chalmers JP (1974) Participation of central serotonergic neurons in the control of the circulation of the unanesthetized rabbit: a study using 5,6–dihydroxytryptamine in experimental neurogenic and renal hypertension. Circ Res 35: 504–513PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heildelberg 1986

Authors and Affiliations

  • P. I. Korner
    • 1
  • E. Badoer
    • 1
  • G. A. Head
    • 1
  1. 1.Baker Medical Research InstitutePrahranAustralia

Personalised recommendations