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Central 5-hydroxytryptamine (5-HT) and its effect on the cardiovascular system

  • A. K. Mir
  • J. R. Fozard
Chapter
Part of the Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine book series (DICM, volume 106)

Abstract

The existence of discrete 5-HT-containing neurones in the brain stem with extensive ramifications to neuroanatomical regions involved in cardiovascular regulation has been known for more than two decades [1]. Our understanding, however, of the intricate interactions of the 5-HT networks and central autonomic pathways has been rather slow to evolve [2–4]. Thus, despite substantial evidence implicating an important role for central 5-HT neurotransmission in blood pressure regulation, the precise nature of this role remains unclear.

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References

  1. 1.
    Dahlstrom A, Fuxe K (1965): Evidence for the existence of monoamine neurones in the central nervous system II. Experimentally induced changes in the intraneouronal amine levels of bulbospinal neurone systems. Acta Physiol Scand 64 (suppl.) 247:5–36.Google Scholar
  2. 2.
    Chalmers JR, Wing LMH (1975): Central serotonin and cardiovascular control. Clin Exp Pharmac Physiol 2 (suppl.): 195 - 200.Google Scholar
  3. 3.
    Korner PI (1971): Integrative neural cardiovascular control. Physiological Reviews 51: 312–367.PubMedGoogle Scholar
  4. 4.
    Chalmers JP, Pilowsky PM, Minson JB, Kapoor V, Mills E, West MJ (1988): Central serotonergic mechanisms in hypertension. Am J Hypertens 1, 79–83.PubMedCrossRefGoogle Scholar
  5. 5.
    Bhargava KP, Tangri KK (1959): The central vasomotor effects of 5-hydroxytryptamine. Br J Pharmacol 14: 411–414.Google Scholar
  6. 6.
    Baum T, Shropshire AT (1975): Inhibition of efferent nerve activity by 5-hydroxytryptophan and centrally administered 5-hydroxytryptamine. Neuropharmacology 14: 227–233.PubMedCrossRefGoogle Scholar
  7. 7.
    Krstic MK, Djurkovic D (1980): Analysis of cardiovascular responses to central administration of 5-hydroxytryptamine in rats. Neuropharmacology 19: 455–463.PubMedCrossRefGoogle Scholar
  8. 8.
    Kuhn DM, Wolf WA, Lovenberg W (1980): Review of the role of the central serotonergic neuronal system in blood pressure regulation. Hypertension 2: 243–255. agonist, causes a biphasic blood pressure response and a bradycardia in the normotensivePubMedCrossRefGoogle Scholar
  9. 9.
    McCall RB, Humphrey ST (1982): Involvement of serotonin in the central regulation of blood pressure: Evidence for a facilitating effect on sympathetic nerve activity. J Pharmacol Exp Ther 222: 94–102.PubMedGoogle Scholar
  10. 10.
    Yusof APM, Coote JH (1988): Excitatory and inhibitory actions of intrathecally administered 5-hydroxytryptamine on sympathetic nerve activity in the rat. J Autonom Nerv Syst 22: 229–236.CrossRefGoogle Scholar
  11. 11.
    Peroutka SJ, Snyder SH (1979): Multiple serotonin receptors: Differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol 16: 687–699.PubMedGoogle Scholar
  12. 12.
    Fozard JR (1987): 5-HT: The enigma variations . Trends Pharmacol Sci 8: 501–506.CrossRefGoogle Scholar
  13. 13.
    Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson B, Saxena PR (1986): Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25: 563–575.PubMedCrossRefGoogle Scholar
  14. 14.
    Richardson BP, Engel G (1986): The pharmacology and function of 5-HT3 receptors. Trends Neurol Sci 5: 424–428.CrossRefGoogle Scholar
  15. 15.
    Fozard JR (1989): Agonists and antagonists for 5-HT3 receptors. Chapter VIII, this volume.Google Scholar
  16. 16.
    Middlemiss DN, Fozard JR (1983): 8-Hydroxy-2-(di-n-propylamino) tetralin discriminates between subtypes of the 5-HT recognition site. Eur J Pharmacol 90:150–153.CrossRefGoogle Scholar
  17. 17.
    Dompert WU, Glaser T, Traber J (1985): 3H-TVX Q 7821: Identification of 5-HT1 binding sites as targets for a novel putative anxiolytic. Naunyn-Schmiedeberg’s Arch Pharmacol 328:467–470.CrossRefGoogle Scholar
  18. 18.
    Hagenbach A, Hoyer D, Kalkman HO, Seiler MP (1986): N-N-propyl-5-carboxamido- tryptamine (DP-5-CT) an extremely potent and selective 5-HT1A agonist. Brit J Pharmacol 87: 136 P.Google Scholar
  19. 19.
    Bevan P, Ramage AG, Wouters W (1986): Investigation of the effects of DU 29373 on the cardiovascular system of the anaesthetised cat. Br J Pharmac 89: 506 P.Google Scholar
  20. 20.
    Fozard JR, Mir AK, Middlemiss DN (1987): The cardiovascular response to 8-hydroxy- 2-(di-n-propylamino) tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis. J Cardiovasc Pharmacol 9: 328–347.PubMedCrossRefGoogle Scholar
  21. 21.
    Hibert M, Mir AK, Maghioros G, Moser P, Middlemiss DN, Tricklebank MD, Fozard JR (1988): The pharmacological properties of MDL 73005 EF: a potent and selective ligand at 5-HT1A receptors. Brit J Pharmacol 93: 2 P.Google Scholar
  22. 22.
    Mir AK, Hibert M, Tricklebank MD, Middlemiss DN, Kidd EJ, Fozard JR (1988): MDL 72832: a potent and stereoselective ligand at central and peripheral 5-HT1A receptors. Eur J Pharmacol 149: 107–120.PubMedCrossRefGoogle Scholar
  23. 23.
    De Voogd JM (1988): Early clinical experience with flesinoxan, a new selective 5-HT1A agonist. Cardiovascular Pharmacology of 5-HT. Amsterdam: October 1988, Abst. P42.Google Scholar
  24. 24.
    Doods HN, Boddeke HWGM, Kalkman HO, Hoyer D, Mathy M-J, Van Zwieten PA (1988): Central 5-HT1A receptors and the mechanism of the central hypotensive effect of (+)8-OH-DPAT, DP-5-CT, R28935, and urapidil. J Cardiovasc Pharmacol 11: 432–437.PubMedCrossRefGoogle Scholar
  25. 25.
    Wouters W, Tulp MTLP, Bevan P (1988): Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors. Eur J Pharmacol 149: 213–223.PubMedCrossRefGoogle Scholar
  26. 26.
    Martin GE, Lis EV (1985): Hypotensive action of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in spontaneously hypertensive rats. Arch Int Pharmacodyn 273: 251–261.PubMedGoogle Scholar
  27. 27.
    Mir AK, Fozard JR (1987): Cardiovascular effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), pp. 120–134 in: Dourish CT, Ahlenius S, Hutson PH (eds), Brain 5-HT1A Receptors. Chichester: Ellis Horwood.Google Scholar
  28. 28.
    Gradin K, Pettersson A, Hedner T, Persson B (1985): Acute administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT receptor Sprague-Dawley rat and the spontaneously hypertensive rat. J Neural Transm 62: 305–319.PubMedCrossRefGoogle Scholar
  29. 29.
    McCall RB, Patel BN, Harris LT (1987): Effects of serotonin and serotonin1 receptor agonists and antagonists on blood pressure, heart rate and sympathetic nerve activity. J Pharmacol Exp Ther 242: 1152–1159.PubMedGoogle Scholar
  30. 30.
    Ramage AG, Fozard JR (1987): Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and ipsapirone, have a central hypertensive action that differs from that of clonidine in anaesthetized cats. Eur J Pharmacol 38: 179–191.CrossRefGoogle Scholar
  31. 31.
    Ramage AG, Wouters W, Bevan P (1988): Evidence that the novel antihypertensive agent flesinoxan causes differential sympathoinhibition and also increases vagal tone by a central action. Eur J Pharmacol 151: 373–379.PubMedCrossRefGoogle Scholar
  32. 32.
    Dalton DW, Feniuk W, Humphrey PPA (1986): An investigation into the mechanisms of the cardiovascular effects of 5-hydroxytryptamine in conscious normotensive and Doca- salt hypertensive rats. J Auton Pharmac 6: 219–229.CrossRefGoogle Scholar
  33. 33.
    Coote JH, Dalton DW, Feniuk W, Humphrey PPA (1987): The central site of the sympatho-inhibitory action of 5-hydroxytryptamine in the cat. Neuropharmacology 26: 147–154.PubMedCrossRefGoogle Scholar
  34. 34.
    Hof R, Fozard JR (1989): 8-OH-DPAT, flesinoxan and guanfacine: systemic and regional haemodynamic effects of centrally acting antihypertensive agents in anaesthetized rabbits. Brit J Pharmacol 96: 864–871.CrossRefGoogle Scholar
  35. 35.
    Mir AK, Hibert M, Fozard JR (1987): Cardiovascular effects of N,N-dipropyl-5-carboxamidotryptamine, a potent and selective 5-HT1A receptor ligand, pp. 21–29 in: Nobin A, Owman C, Arneklo-Nobin B (eds.), Neuronal Messengers in Vascular Function. Amsterdam: Elsevier.Google Scholar
  36. 36.
    Fozard JR, Mir AK, Ramage AG (1989): 5-HT1A receptors and cardiovascular control, pp. 146–151, in Mylecharane EJ, Angus JA, De La Lande IS, Humphrey PPA (eds), Serotonin: Actions, Receptors, Pathophysiology. Proceedings of the 1987 IUPHAR Congress Satellite Meeting, Heron Island, Australia: London, MacMillan.Google Scholar
  37. 37.
    Dreteler GH, Wouters W, Saxena PR (1988): The effect of putative 5-HT1A antagonists on the cardiovascular response to flesinoxan in the rat. Cardiovascular Pharmacology of 5-HT, Amsterdam, October 1988, Abst. p. 34.Google Scholar
  38. 38.
    Dabire H, Cherqui C, Fournier B, Schmitt H (1987): Comparison of effects of some 5-HT1 agonists on blood pressure and heart rate of normotensive anaesthetized rats. Europ J Pharmacol 140: 259–266.CrossRefGoogle Scholar
  39. 39.
    Van Zwieten PA, De Jonge A, Wilffert B, Timmermans PBM WM, Beckeringh JJ, Thoolen MJMC (1985): Cardiovascular effects and interaction with adrenoceptors of urapidil. Arch Int Pharmacodyn Ther 276: 180–201.PubMedGoogle Scholar
  40. 40.
    Fozard JR, Mir AK (1987): Are 5-HT1A receptors involved in the antihypertensive effects of urapidil? Br J Pharmac 90: 24 P.Google Scholar
  41. 41.
    Gross G, Hanft G, Kolassa N (1987): Urapidil and some analogues with hypotensive properties show high affinity for 5-hydroxytryptamine (5-HT) binding sites of the 5-HT1A subtype and for α1-adrenoceptor binding sites. Naunyn-Schmiedeberg’s Arch Pharmacol 336: 597–601.CrossRefGoogle Scholar
  42. 42.
    Sanders KH, Jurna I (1985): Effects of urapidil, clonidine, prazosin and propranolol on autonomic nerve activity, blood pressure and heart rate in anaesthetized rats and cats. Eur J Pharmacol 110: 181–190.PubMedCrossRefGoogle Scholar
  43. 43.
    Ramage AG (1986): A comparison of the effects of doxazosin and alfuzosin with those of urapidil on preganglionic sympathetic nerve activity in anaesthetised cats. Eur J Pharmac 129: 307–314.CrossRefGoogle Scholar
  44. 44.
    Ramage AG (1988): Are drugs that act both on serotonin receptors and α1-adrenoceptors more potent hypotensive agents than those that act only on α1-adrenoceptors? J Cardiovasc Pharmac 11 (suppl. 1): S30– S34.CrossRefGoogle Scholar
  45. 45.
    Kolassa N, Beller K-D, Bischler P, Kowallik P, Sanders KH (1988): Central serotonin- lA-receptor mediated hypotensive response to urapidil after peripheral administration. Cardiovascular pharmacology of 5-HT. Amsterdam October 1988, Abst. P27.Google Scholar
  46. 46.
    Ramage AG (1989): Evidence that spiperone reverses the additional sympathoinhibitory action of urapidil in anaesthetised prazosin pretreated cats. Chapter XXIX, this volume.Google Scholar
  47. 47.
    Tricklebank MD (1985): The behavioural response to 5-HT receptor agonists and subtypes of the central 5-HT receptor. Trends Pharmacol Sci 6: 403–407.CrossRefGoogle Scholar
  48. 48.
    Berger A, Ramirez AJ (1988): Hypotensive spinal serotonergic effects are S1 and S2 receptors involved? Hypertension 11 (suppl. 1): 182–185.CrossRefGoogle Scholar
  49. 49.
    Kadzielawa K (1983): Antagonism of the excitatory effects of 5-hydroxytryptamine on sympathetic preganglionic neurones and neurones activated by visceral afferents. Neuropharmacology 22: 19–27.PubMedCrossRefGoogle Scholar
  50. 50.
    McCall RB (1984): Evidence for a serotonergic mediated sympathoexcitatory responses to stimulation of medullary raphe nuclei. Brain Res 311: 131–139.PubMedCrossRefGoogle Scholar
  51. 51.
    McCall, RB (1983): Serotonergic excitation of sympathetic preganglionic neurons: microiontophoretic study. Brain Res 289: 121–127.PubMedCrossRefGoogle Scholar
  52. 52.
    McCall RB, Harris LT (1988): 5-HT2 receptor agonists increase spontaneous sympathetic nerve activity. Eur J Pharmacol 151:113–116.PubMedCrossRefGoogle Scholar
  53. 53.
    Antonaccio MJ, Taylor DG (1977): Reduction in blood pressure, sympathetic nerve discharge and central evoked pressor response by methysergide in anaesthetised cats. Eur J Pharmacol 42: 331–338.PubMedCrossRefGoogle Scholar
  54. 54.
    Tadepalli AS, Ho KW, Buckley JP (1979): Enhancement of reflex bradycardia following intracerebroventricular administration of methysergide in cats. Eur J Pharmacol 69: 85–93.CrossRefGoogle Scholar
  55. 55.
    Ramage AG (1985): The effects of ketanserin, methysergide and LY 53857 on sympathetic nerve activity. Eur J Pharmacol 113: 295–303.PubMedCrossRefGoogle Scholar
  56. 56.
    McCall RB and Schuette MR (1984): Evidence for an alpha, receptor mediated central sympathoinhibitory action of ketanserin. J Pharmacol Exp Ther 228: 704–710.PubMedGoogle Scholar
  57. 57.
    McCall RB, Harris DT (1987): Characterization of the central sympathoinhibitory action of ketanserin. J. Pharmacol Exp Ther 241: 736–740.PubMedGoogle Scholar
  58. 58.
    Fozard JR (1982): Mechanism of the hypotensive effect of ketanserin. J Cardiovasc Pharmacol 4: 829–838.PubMedCrossRefGoogle Scholar
  59. 59.
    Kalkman HO, Harms YM, Gelderen VM, van Batink HD, Timmermans PBMWM, Van Zwieten RA (1983): Hypotensive activity of serotonin antagonists; correlation with α1-adrenoceptor and serotonin receptor blockade. Life Sci 32: 1499–1505.PubMedCrossRefGoogle Scholar
  60. 60.
    Cohen MD, Fuller RW, Kurz KD (1983): Evidence that blood pressure reduction by serotonin antagonists is related to alpha receptor blockade in spontaneously hypertensive rats. Hypertension 5: 676–681.PubMedCrossRefGoogle Scholar
  61. 61.
    Ramage AG (1988): Examination of the effects of some 5-HT2 receptor antagonists on central sympathetic outflow and blood pressure in anaesthetised cats. Naunyn- Schmiedeberg’s Arch Pharmacol 338: 601–607.CrossRefGoogle Scholar
  62. 62.
    Cohen ML, Fuller RW, Kurz KD (1983): LY 53857, a selective and potent serotonergic (5-HT2) receptor antagonist, does not lower blood pressure in the spontaneously hypertensive rats. J Pharmacol Exp Ther 227: 327–332.PubMedGoogle Scholar
  63. 63.
    Vanhoutte PM, Ball SG, Berdeaux A, Cohen MD, Hedner T, McCall R, Ramage AG, Reimann IH, Richer C, Saxena PR, Schalekamp MADH, Struyker-Boudier HAJ, Symoens J, Van Neuten JM, Van Zwieten RA (1986): Mechanism of action of ketanserin in hypertension. Trends Pharmacol Sci 7: 58–59.CrossRefGoogle Scholar
  64. 64.
    Hedner T, Persson B (1988): Experience with ketanserin and ritanserin in hypertensive patients. J Cardiovasc Pharmacol 11 (suppl. 1): S44– S48.PubMedCrossRefGoogle Scholar
  65. 65.
    Scott AK, Chaudhury PR, Webster J, Petrie JC (1988): Selective 5-HT antagonist (ICI 169,369): lack of effect on blood pressure in hypertensive patients. Brit J Clin Pharmacol 25: P651.Google Scholar
  66. 66.
    Hoyer D (1989): Biochemical mechanisms of 5-HT receptor-effector coupling in peripheral tissues, pp. 72–99 in: Fozard JR (ed.), The Peripheral Actions of 5-hydroxy- tryptamine. Oxford University Press.Google Scholar
  67. 67.
    Di Francesco GF, Petty MA, Fozard JR (1988): Antihypertensive effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in conscious dogs. Eur J Pharmacol 147: 287 - 290.PubMedCrossRefGoogle Scholar
  68. 68.
    Wouters W, Bevan P (1988): 5-HT related drugs and hypertension. Cardiovascular pharmacology of 5-HT, Amsterdam October 1988, Abst. S23.Google Scholar

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© Springer Science+Business Media Dordrecht 1990

Authors and Affiliations

  • A. K. Mir
  • J. R. Fozard

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