Centrally Acting Drugs as a Tool to Study Central Mechanisms of Blood Pressure Control

  • W. Hoefke
  • W. Gaida
Part of the Current Topics in Neuroendocrinology book series (CT NEUROENDOCRI, volume 3)

Abstract

The importance of adrenergic and of serotonergic mechanisms and of gamma-amino-butyric acid in regulating blood pressure is reviewed in this article using centrally acting antihypertensive agents as tools. Details on physiological aspects of blood pressure control have been reviewed by Chalmers (1975) or Korner and Angus (1981).

Keywords

Dopamine Serotonin Noradrenaline Adrenaline Fluoxetine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Antonaccio MJ, Halley J (1976) Studies on the mechanism and brainstem site of action of the hypotensive, bradycardic and reflex-enhancing actions of clonidine in cats. Fed Proc 35:323Google Scholar
  2. Antonaccio MJ, Robson RD (1973) Cardiovascular effects of 5-hydroxytryptophan in anaesthetized dogs. J Pharmacol 25:495–497Google Scholar
  3. Antonaccio MJ, Taylor DG (1977a) Reduction in blood pressure, sympathetic nerve discharge and centrally evoked pressor responses by methysergide in anaesthetized cats. Eur J Pharmacol 42:331–338PubMedGoogle Scholar
  4. Antonaccio MJ, Taylor DG (1977b) Involvement of central GABA receptors in the regulation of blood pressure and heart rate of anaesthetized cats. Eur J Pharmacol 46:283–287PubMedGoogle Scholar
  5. Antonaccio MJ, Kelly E, Halley J (1975) Centrally mediated hypotension and bradycardia by methysergide in anaesthetized dogs. Eur J Pharmacol 33:107–117PubMedGoogle Scholar
  6. Antonaccio MJ, Kerwin L, Taylor DG (1978) Effects of central GABA receptor agonism and antagonism on evoked diencephalic cardiovascular responses. Neuropharmacology 17:597–603PubMedGoogle Scholar
  7. Awapara J, Landon AJ, Fuerst R, Seale B (1950) Free γ-amino-butyric acid in brain. J Biol Chem 187:35–39PubMedGoogle Scholar
  8. Baum T, Becker FT (1982a) Hypotensive and postural effects of the γ-aminobutyric acid agonist muscimol and of clonidine. J Cardiovasc Pharmacol 4,2:165–169PubMedGoogle Scholar
  9. Baum T, Becker FT (1982b) Alpha-adrenergic and 5-hydroxytryptaminergic receptor stimulants as new antihypertensive drugs with observations on involvement of opiate receptors. Clin Exp Hypertens - Theory and Practice A4 (1–2):235–248Google Scholar
  10. Baum T, Shropshire AT (1973) Reduction of sympathetic outflow by central administration of L-dopa, dopamine and norepinephrine. Neuropharmacology 12:49–56PubMedGoogle Scholar
  11. Baum T, Shropshire AT (1975) Inhibition of efferent sympathetic nerve activity by 5-hydroxytryptophan and centrally administered 5-hydroxytryptamine. Neuropharmacology 14:227–233PubMedGoogle Scholar
  12. Berthelsen S, Pettinger WA (1977) A functional basis for classification of α-adrenergic receptors. Life Sci 21:595–606PubMedGoogle Scholar
  13. Bhargava KP, Tangr K (1959) The central vasomotor effect of 5-hydroxytryptamine. Br J Pharmacol 14:411–414Google Scholar
  14. Bhargava KP, Bhattacharya SS, Srimal RC (1964) Central cardiovascular actions of γ-aminobutyric acid. Br J Pharmacol 23:383–390Google Scholar
  15. Blessing WW, Chalmers JP (1979) Direct projections of dopaminergic neurons from hypothalamus to spinal cord. Neurosci Lett 11:35–40PubMedGoogle Scholar
  16. Bobillier P, Seguin S, Petitjean F, Salvert D, Touret M, Jouvet M (1976) The raphe nuclei of the cat brain stem: A topographical atlas of their efferent projections as revealed by autoradiography. Brain Res 113:449–486PubMedGoogle Scholar
  17. Boissier JR, Giudicelli JF, Fichelle J, Schmitt H, Schmitt H (1968) Cardiovascular effects of 2-(2,6-dichlorphenylamino)-2-imidazoline hydrochloride (St 155). I. Peripheral sympathetic system. Eur J Pharmacol 2:333–339PubMedGoogle Scholar
  18. Bolme P, Fuxe K (1977) Possible involvement of GABA mechanisms in central cardiovascular and respiratory control. Studies on the interaction between diazepam, picrotoxin, and clonidine. Med Biol 55:301–309PubMedGoogle Scholar
  19. Bolme P, Corrodi H, Fuxe K, Hökfelt T, Lidbrink P, Goldstein M (1974) Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Eur J Pharmacol 28:89–94PubMedGoogle Scholar
  20. Bousquet P, Guertzenstein PG (1973) Localization of the central cardiovascular action of clonidine. Br J Pharmacol 49:573–579PubMedGoogle Scholar
  21. Bousquet P, Feldman J, Bloch R, Schwartz J (1981a) The nucleus reticularis lateralis: A region highly sensitive to clonidine. Eur J Pharmacol 69:389–392PubMedGoogle Scholar
  22. Bousquet P, Feldman J, Bloch R, Schwartz J (1981b) The ventromedullary hypotensive effect of muscimol in the anaesthetized cat. Clin Exp Hypertens 3(2): 195–205PubMedGoogle Scholar
  23. Buckingham RE, Hamilton TC, Robson D (1976) Effect of intracerebroventricular 5,6-dihydroxytryptamine on blood pressure of spontaneously hypertensive rats. Eur J Pharmacol 36:431–437PubMedGoogle Scholar
  24. Carlsson A, Lindqvist M (1962) In-vivo decarboxylation of a-methyl dopa and α-me-thyl metatyrosine. Acta Physiol Scand 54:87–94PubMedGoogle Scholar
  25. Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-dihydroxyphenylamine and 5-hydroxytryptophan as reserpine antagonists. Nature 180:1200nPubMedGoogle Scholar
  26. Cavero I, Roach AG (1980) Effects of clonidine on canine cardiac neuroeffector structures controlling heart rate. Br J Pharmacol 70:269–276PubMedGoogle Scholar
  27. Cedarbaum JM, Aghajanian GK (1976) Noradrenergic neurons of the locus coeruleus: Inhibition of epinephrine and activation by the a-antagonist piperoxan. Brain Res 112:413PubMedGoogle Scholar
  28. Chahl LA, Walker SB (1980) The effect of baclofen on the cardiovascular system of the rat. Br J Pharmacol 69:631–637PubMedGoogle Scholar
  29. Chalmers JP (1975) Neuropharmacology of central mechanisms regulating pressure. In: Davies DS, Reid JL (eds) Central action of drugs in blood pressure regulation. Pitman Medical, London, pp 36–59Google Scholar
  30. Chase LK, Ng TN, Colburn RW, Kopin IJ (1972) Release of (3H) dopamine by L-5-hydroxytryptophan. Brain Res 45:499–505PubMedGoogle Scholar
  31. Cheramy E, Nieoullon A, Glowinski J (1978) GABA-ergic processes involved in the control of dopamine release from nigrostriatal dopaminergic neurons in the cat. Eur J Pharmacol 48:281–295PubMedGoogle Scholar
  32. Collis MG, Vanhoutte PM (1977) Vascular reactivity of isolated perfused kidneys from male and female spontaneously hypertensive rats. Circ Res 41:759–767PubMedGoogle Scholar
  33. Collis MG, Vanhoutte PM (1981) Studies on the mechanism of tachyphylaxis to 5-hydroxytryptamine in perfused kidneys from spontaneously hypertensive and normotensive rats. J Cardiovasc Pharmacol 3:229–235PubMedGoogle Scholar
  34. Constantine JW, McShane WK (1968) Analysis of the cardiovascular effects of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (Catapres). Eur J Pharmacol 4:109–123PubMedGoogle Scholar
  35. Costa E (1981) Molecular mechanisms for the modulation of GABAergic transmission. Proc Int Workshop Neuropharmacology, Taipei 1981. In: Lee CY (ed) Advances in neuropharmacology. Academia Simica, Taipei, pp 123–131Google Scholar
  36. Costall B, Naylor RJ (1981) Minireview: The hypothesis of different dopamine receptor mechanisms. Life Sci 28:215–229PubMedGoogle Scholar
  37. Crawley JN, Maas JW, Roth RH (1980) Evidence against specificity of electrical stimulation of the nucleus locus coeruleus in activating the sympathetic nervous system in the rat. Brain Res 183:301–311PubMedGoogle Scholar
  38. Curtis DR (1979) GABAergic transmission in the mammalian central nervous system. In: Krogsgaard-Larsen P, Scheel-Krüger J, Kofod H (eds) GABA-neurotransmitters. Munksgaard, Copenhagen, pp 17–27Google Scholar
  39. Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. Acta Physiol Scand 62 [Suppl] 232:50–51Google Scholar
  40. Dahlström A, Fuxe K (1965) Evidence for the existence of monoamine neurons in the central nervous system: II. Experimental induced changes in the intraneuronal amine levels of bulbospinal neuron system. Acta Physiol Scand 64 [Suppl] 247: 1–36Google Scholar
  41. Davies J, Watkins JC (1974) The action of β-phenyl-GABA derivatives on neurons of the cat cerebral cortex. Brain Res 70:501–505PubMedGoogle Scholar
  42. Day MD, Rand MJ (1963) A hypothesis for the mode of action of a-methyldopa in relieving hypertension. J Pharmacol 15:221–224Google Scholar
  43. De Cree J, Geukens H, De Cock W, Verhaegen H (1981) The antihypertensive effects of a new selective 5-HT2-receptor blocking agent (R41 468). Eighth Scientific Meeting of the International Society of Hypertension, Milan, Italy, Abstract 351Google Scholar
  44. De Feudi FV (1981) Recent studies on the pharmacology of GABA: therapeutic perspectives. TIPS, May VI-IXGoogle Scholar
  45. de Jong W (1974) Noradrenaline central inhibitory control of blood pressure and heart rate. Eur J Pharmacol 29:179–181PubMedGoogle Scholar
  46. de Jong W, Nijkamp FP (1976) Centrally induced hypotension and bradycardia after administration of alpha-methyl-noradrenaline into the area of the nucleus tractus soltiarii of the rat. Br J Pharmacol 58:593–598PubMedGoogle Scholar
  47. Dhumal VR, Gulati AA, Bhavsar VH (1980) Central hypotensive effect of γ-amino-butyric acid in anaesthetized dogs. J Pharm Pharmacol 32:724–725PubMedGoogle Scholar
  48. DiMicco JA (1978) Neurocardiovascular effects of the GABA antagonists picrotoxin and bicuculline in the cat: evidence for involvement of GABA in central cardiovascular control. P. Thesis, Georgetown UniversityGoogle Scholar
  49. DiMicco JA, Prestel T, Pearl DL (1976) Cardiovascular changes produced by stimulation of the central nervous system with picrotoxin. Fed Proc 35:981Google Scholar
  50. Doba N, Reis DJ (1973) Acute fulminating neurogenic hypertension produced by brainstem lesions in the rat. Circ Res 32:584–593PubMedGoogle Scholar
  51. Doherty JD, Hattox SE, Snead OC, Roth RH (1978) Identification of endogenous γ-hydroxybutyrate in human and bovine brain and its regional distribution in human, guinea pig and rhesus monkey brain. J Pharmacol Exp Ther 207:130–139PubMedGoogle Scholar
  52. Dollery CT, Reidl JL (1973) Central noradrenergic neurones and the cardiovascular actions of clonidine in the rabbit. Br J Pharmacol 47:206–216PubMedGoogle Scholar
  53. Dunkley B, Sanghvi I, Friedman E, Gershon S (1972) Comparison of behavioral and cardiovascular effects of L-Dopa and 5-HTP in conscious dogs. Psychopharmacol (Berlin) 26:161–172Google Scholar
  54. Ehringer H, Hornykiewicz O (1960) Verteilung von Noradrenalin und Dopamin (3-Hydroxy-tyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin Wochenschr 38:1236–1239PubMedGoogle Scholar
  55. Elliot KAC, Hobbiger F (1959) Gamma aminobutyric acid: Circulatory and respiratory effects in different species; reinvestigation of the anti-strychnine action in mice. J Physiology 146:70–84Google Scholar
  56. Enna SJ (1981) GABA receptors. TIPS March:62–64Google Scholar
  57. Enna SJ, Maggi A (1979) Minireview: Biochemical pharmacology of GABAergic agonists. Life Sci 24:1727–1738PubMedGoogle Scholar
  58. Falck B, Hillarp NA, Thieme G, Torp A (1962) Fluorescence of catecholamines and related compounds with formaldehyde. J Histochem Cytochem 10:348–354Google Scholar
  59. Finch L (1975) The cardiovascular effects of intraventricular 5,6-dihydroxytrypt-amine in conscious rats. Clin Exp Pharmacol Physiol 2:503–505PubMedGoogle Scholar
  60. Feuerstein G, Yamaguchi I, Kopin IJ (1981) Effect of GABA agonists and antagonists on cardiovascular and sympathetic responses in SHR and WKY rats. Clin Exp Hypertens 3(2):207–218PubMedGoogle Scholar
  61. Florez J, Armigo JA (1974) Effect of central inhibition of the l-aminoacid decarboxylase on the hypertensive action of 5-HT precursors in rats. Eur J Pharmacol 26: 108–110PubMedGoogle Scholar
  62. Fuentes JA, Ordaz A, Neff NH (1979) Central mediation of the antihypertensive effect of pargyline in spontaneously hypertensive rats. Eur J Pharmacol 57:21–27PubMedGoogle Scholar
  63. Fuller RW, Holland OR, Yen TJ, Bemis KG, Stamm NB (1979) Antihypertensive effects of fluoxetine and 1,5-hydroxytryptophan in rats. Life Sci 25:1237–1242PubMedGoogle Scholar
  64. Fuller RW, Yent TT, Stamm NB (1981) Lowering on blood pressure by direct and indirect acting serotonin in spontaneously hypertensive rats. Clin Exp Hypertens 3(3):497–508PubMedGoogle Scholar
  65. Fuxe K (1965) Evidence for the existence of monoamine neurons in the CNS. IV. The distribution of monoamine terminals in the CNS. Acta Physiol Scand 64 [Suppl 247]:38–85Google Scholar
  66. Gaddum JH, Picarelli ZP (1957) Two kinds of tryptamine receptors. Br J Pharmacol 12:323–328Google Scholar
  67. Gillis R, Williford DJ, Souza JD, Quesi JA (1982) Central cardiovascular effects produced by the GABA receptor agonist drug THIP. Neuropharmacology 21: 595–597Google Scholar
  68. Goldberg LI (1972) Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev 24:1–29PubMedGoogle Scholar
  69. Gomes C, Flygt C, Henning M, Norin L, Svensson TH, Trolin G (1976) Gamma-hydroxybutyric acid: Cardiovascular effects in the rat. J Neural Transm 38:123–129PubMedGoogle Scholar
  70. Gothert M, Klupp N (1978) Cardiovascular effects of neurotoxic indolethylamines. Ann NY Acad Sci 305:457–477PubMedGoogle Scholar
  71. Greenberg DA, U’Prichard DC, Snyder SH (1976) Alpha-noradrenergic receptor binding in mammalian brain: Different labelling of agonist and antagonist states. Life Sci 19:69–76PubMedGoogle Scholar
  72. Gyermek L (1961) 5-Hydroxytryptamine antagonists. Pharmacol Rev 13:399–439PubMedGoogle Scholar
  73. Haeusler G (1974) Further similarities between the action of clonidine and a central activation of the depressor baroreceptor reflex. Naunyn Schmiedebergs Arch Pharmacol 285:1–14PubMedGoogle Scholar
  74. Haeusler G (1982) Central a-adrenoceptors involved in cardiovascular regulation. J Cardio vase Pharmacol 4:S72-S76Google Scholar
  75. Haeusler G, Finch L (1972) On the nature of the central hypotensive effect of clonidine and α-methyldopa. J Pharmacol (Paris) 3:544–545Google Scholar
  76. Heise A (1976) Hypotensive action by central α-adrenergic and dopaminergic receptor stimulation. In: Scriabine A, Sweet CS (eds) New antihypertensive drugs. Chronographs of the Physiological Society of Philadelphia, vol 2. Spectrum, New York, pp 135–145Google Scholar
  77. Heise A, Kroneberg G (1973) Central nervous α-adrenergic receptors and the mode of action of α-methyldopa. Naunyn Schmiedebergs Arch Pharmacol 279:285–300PubMedGoogle Scholar
  78. Heller H (1933) Über die zentrale Blut druck Wirkung des Adrenalins. Naunyn Schmiedebergs Arch Exp Pathol 173:291–300Google Scholar
  79. Henning M, Rubenson A (1970) Central hypotensive effect of L-3,4-dihydroxyphenyl-alanine in the rat. J Pharm Pharmac 22:553–560Google Scholar
  80. Henning M, van Zwieten PA (1967) Central hypotensive effect of α-methyldopa. J Pharm Pharmac 19:403–405Google Scholar
  81. Henning M, Rubenson A, Trolin G (1972) On the localization of the hypotensive effect of L-dopa. J Pharm Pharmac 24:447–451Google Scholar
  82. Higgins CB, Millard RW, Braunwald E, Vatner SF (1973) Effects and mechanisms of action of dopamine on regional hemodynamics in the conscious dog. Am J Physiol 255:423–437Google Scholar
  83. Ho IK, Habeshima T, Sivam SP, Flint BA, Hoskins B (1981) Effects of pentobarbital on GABA system. Proc Int Workshop Neuropharmacology, Teipei 1981. In: Lee CY (ed) Advances in Neuropharmacology. Academia Simica, Teipei, pp 133–140Google Scholar
  84. Hoefke W (1976) Centrally acting antihypotensive agents. In: Engelhardt EL (ed) ACS Symposium Series 27, Antihypotensive agents. Am Chemical Society, Washington, pp 27–54Google Scholar
  85. Hoefke W, Jennewein HM (1981) Mechanisms of antihypertensive action of clonidine in relation to its psychotropic effects. Psychopharmacology of clonidine. Liss, New York, pp 75–97Google Scholar
  86. Hoefke W, Kobinger W (1966) Pharmakologische Wirkungen des 2-(2,6-Dichlorphenyl-amino)-2-imidazolinhydrochlorids, einer neuen, antihypertensiven Substanz. Arzneim Forsch 16:1038–1050Google Scholar
  87. Hoefke W, Kobinger W (1967) Pharmakologische Wirkungen eines neuen Antihypertensivums mit Imidazolin-Struktur. Naunyn Schmiedebergs Arch Pharmacol 257: 28–29Google Scholar
  88. Hoefke W, Gaida W, Rominger KL (1979) Blood pressure, heart rate and urinary catecholamines after stopping treatment with antihypertensive agents in rats. In: Sixth Scientific Meeting of the International Society of Hypertension, Göteborg, Sweden. Abstracts 252Google Scholar
  89. Hökfelt B, Hedeland H, Dymling J-F (1970) Studies on catecholamines, renin and aldosterone following Catapresan (2-(2,6-dichlorphenylamine)-2-imidazoline hydrochloride) in hypertensive patients. Eur J Pharmacol 10:389–397PubMedGoogle Scholar
  90. Hökfelt T, Fuxe K, Goldstein M, Johannsson O (1974) Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain. Brain Res 66:235–251Google Scholar
  91. Hökfelt T, Johansson O, Fuxe K, Goldstein M, Park D (1976) Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain. I. Tyrosine hydroxylase in the mes- and diencephalon. Med Biol 54: 427–453PubMedGoogle Scholar
  92. Holtz P (1950) Über die sympathomimetische Wirksamkeit von Gehirnextrakten. Acta Physiol Scand 20:354–362PubMedGoogle Scholar
  93. Holtz P, Credner K, Kronberg G (1944/47) Über das sympathicomimetische pressorische Prinzip des Harns („Urosympathin”). Naunyn Schmiedebergs Arch Exp Pathol 804:228–243Google Scholar
  94. Hong E, Nava-Felix P, Vidrio H (1978) On the central antihypertensive effects of a new tryptamine derivative. Pharmacologist 20(3): 188Google Scholar
  95. Hong E, Rion R, Nava-Felix P (1979) Presynaptic receptor stimulation induced by the central antihypertensive 5-methoxytryptamine, β-methylcarboxylate (TR 3369). Pharmacologist 21:254Google Scholar
  96. Horwitz D, Sjoerdsma A (1964) Effects of alpha-methyl-meta-tyrosine intravenously in man. Life Sci 3:41–48PubMedGoogle Scholar
  97. Howe PRC, Stead BH, Chalmers JP (1982) Central serotonin nerves in spontaneously hypertensive and Doca-salt hypertensive rats. Hypertensive mechanisms. In: Rascher W, Clough D, Ganten D (eds) The spontaneously hypertensive rat as a model to study human hypertension. Schattauer, Stuttgart, pp 627–631Google Scholar
  98. Hukuhara T Jr, Otsuka Y, Takeda R, Sakai F (1968) Die zentralen Wirkungen des 2-(2,6-Dichlorphenylamino)-2-imidazn-hydrochlorids. Arzneim Forsch 18:1147–1153Google Scholar
  99. Ingenito AJ, Barrett JP, Procita L (1970) A centrally mediated peripheral hypotensive effect of a-methyldopa. J Pharmacol Exp Ther 175:593PubMedGoogle Scholar
  100. Ito A, Schanberg SM (1972) Central nervous system mechanisms responsible for blood pressure elevation induced by p-chlorophenylalanine. J Pharmacol Exp Ther 181: 65–74PubMedGoogle Scholar
  101. Iversen LL (1978) Biochemical psychopharmacology of GABA. In: Lipton MA, Di-Mascio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven Press, New York, pp 25–38Google Scholar
  102. Johnston GAR, Willow M (1982) GABA and barbiturate receptors. TIPS Aug:328–330Google Scholar
  103. Kebanian JW, Calm DB (1979) Multiple receptors for dopamine. Nature 277:93–96Google Scholar
  104. Kobinger W (1967) Über den Wirkungsmechanismus einer neuen antihypertensiven Substanz mit Imidazolinstruktur. Naunyn Schmiedebergs Arch Pharmacol 258: 48–58Google Scholar
  105. Kobinger W, Hoefke W (1968) Pharmakologische Untersuchungen über den Angriffspunkt und Wirkungsmechanismus eines neuen Hochdruckmittels. In: Heilmeyer F, Holtmeier H-J, Pfeiffer EF (eds) Hochdrucktherapie. Thieme, Stuttgart, pp 4–17Google Scholar
  106. Kobinger W, Pichler L (1975a) The central modulatory effect of Clonidine on the cardiopressor reflex after suppression of synthesis and storage of noradrenaline. Eur J Pharmacol 3 0:56–62Google Scholar
  107. Kobinger W, Pichler L (1975b) Localization in the CNS of adrenoceptors which facilitate a cardioinhibitory reflex. Naunyn Schmiedebergs Arch Pharmacol 286: 371–377PubMedGoogle Scholar
  108. Kobinger W, Walland A (1967a) Kreislaufuntersuchungen mit 2-(2,6-Dichlorphenyl-amino)-2-imidazolin-hydrochlorid. Arzneim Forsch 17:292–300Google Scholar
  109. Kobinger W, Walland A (1967b) Investigations into the mechanism of the hypotensive effect of 2-(2,6-dichlorphenylamino)-2-imidazoline-HCl. Eur J Pharmacol 2:155–162PubMedGoogle Scholar
  110. Kobinger W, Walland A (1971) Involvement of adrenergic receptors in central vagus activity. Eur J Pharmacol 16:120–122Google Scholar
  111. Kobinger W, Walland A (1972) Evidence for a central activation of a vagal cardio-depressor reflex by clonidine. Eur J Pharmacol 19:203–209PubMedGoogle Scholar
  112. Korner PI, Angus JA (1981) Central nervous control of blood pressure in relation to antihypertensive drug treatment. Pharmac Ther 13:231–356Google Scholar
  113. Krstic MK, Djurkovic D (1980) Analysis of cardiovascular responses to central administration of 5-hydroxytryptamine in rats. Neuropharmacology 19:455–463PubMedGoogle Scholar
  114. Kuhn DM, William A, Wolf BA, Lovenberg W (1980) Review of the role of the central serotonergic neuronal system in blood pressure regulation. Hypertension 2:243–255PubMedGoogle Scholar
  115. Lambert G, Friedman E, Gershon S (1975) Centrally mediated cardiovascular response to 5-HT. Life Sci 17:915–920PubMedGoogle Scholar
  116. Lambert GA, Friedman E, Buchweitz E, Gershon S (1978) Involvement of 5-hydroxytryptamine in the central control of respiration, blood pressure and heart rate in the anaesthetized rat. Neuropharmacology 17:807–813PubMedGoogle Scholar
  117. Lang WJ, Woodman OL (1979) Cardiovascular responses produced by the injection of dopamine into the cerebral ventricles ofthe unanaesthetized dog. Br J Pharmacol 66:235–240PubMedGoogle Scholar
  118. Laubie M, Schmitt H (1977) Sites of action of clonidine: centrally mediated increase in vagal tone, centrally mediated hypotensive and sympatho-inhibitory effects. In: de Jongh W, Provoost AP, Shapiro AP (eds) Hypertension and brain mechanisms. Elsevier, Amsterdam, pp 337–348Google Scholar
  119. Laubie M, Delbarre B, Bogaievsky D, Bogaievsky Y, Tsoucaris-Kupfer D, Senon D, Schmitt H (1976a) Pharmacological evidence for a central alpha-sympathomimetic mechanism controlling blood pressure and heart rate. Circ Res [Suppl III] 38: 35–41PubMedGoogle Scholar
  120. Laubie M, Schmitt H, Drouillat M (1976b) Action of clonidine on the baroreceptor pathway and medullary sites mediating vagal bradycardia. Eur J Pharmacol 38: 293–303PubMedGoogle Scholar
  121. Leysen JE, Awouters F, Kennis L, Ladaron J, Vandenberg J, Janssen PAJ (1981) Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci 28:1015–1022PubMedGoogle Scholar
  122. Lipski J, Przybylski J, Solnicka E (1975) Reduced hypotensive effect of clonidine after lesions of the nucleus tractus solitarii in rats. Eur J Pharmacol 38:19–22Google Scholar
  123. Lokhandwala MF (1979) Analysis of the effect of bromocriptine on blood pressure and sympathetic nerve function. Eur J Pharmacol 56:253–256PubMedGoogle Scholar
  124. Lovenberg W, Wolf W, Kuhn D (1982) The central serotonergic neuronal system and blood pressure regulation in the spontaneous hypertensive rats. Hypertensive mechanisms. In: Rascher W, Clough D, Ganten D (eds) The spontaneous hypertensive rat as a model to study human hypertension. Schattauer, Stuttgart, pp 632–637Google Scholar
  125. Martinez AA, Lokhandwala MF (1980) Evidence for a presynaptic inhibitory action of 5-hydroxytryptamine on sympathetic neurotransmission to the myocardium. Eur J Pharmacol 63:303–311PubMedGoogle Scholar
  126. McCall RB, Humphrey SJ (1982) Involvement of serotonin in the central regulation of blood pressure: evidence for a facilitating effect on sympathetic nerve activity. J Pharmacol Exp Ther 222:94–102PubMedGoogle Scholar
  127. McCubbin IW, Kameko Y, Page IH (1960) Ability of serotonin and norepinephrine to mimic the central effects of reserpine on vasomotor activity. Circ Res 8:849–858PubMedGoogle Scholar
  128. McGeer EG, McGeer PL (1979) GABA-containing neurons in schizophrenia. Huntington’s chorea and normal agint. In: Krogsgaard-Larsen P, Scheel-Kriiger J, Kofod H (eds) GABA-neurotransmitters. Munksgaard, Copenhagen, pp 340–356Google Scholar
  129. McMurtry JP, Kazama N, Wexler BC (1979) Effects of bromocriptine on hormone and blood pressure levels in the spontaneous hypertensive rat. Proc Soc Exp Biol Med 161:186–188PubMedGoogle Scholar
  130. Meldrum BS (1975) Epilepsy and GABA-mediated inhibition. Int Rev Neurobiol 17: 1–36PubMedGoogle Scholar
  131. Müller GF, Eugster CH (1965) Muscimol, ein pharmakodynamisch wirksamer Stoff aus Amanita muscaria. Helv Chim Acta 48:910–926Google Scholar
  132. Nagaoka A, Lovenberg W (1977) Regional changes in the activities of aminergic biosynthetic enzymes in the brain of hypertensive rats. Eur J Pharmacol 43:297–306PubMedGoogle Scholar
  133. Nava-Felix P, Hong E (1979) Nature of the central serotonin receptors mediating hypotension. J Cardiovasc Pharmacol 1:461–466PubMedGoogle Scholar
  134. Nayler WG, Price JM, Swann JB, McInnes I, Race D, Lowe TE (1968) Effect of the hypotensive drug St 155 (Catapres) on the heart and peripheral circulation. J Pharmacol Exp Ther 164:45–59PubMedGoogle Scholar
  135. Nijkamp FP, de Jong W (1975) Alpha-methylnoradrenaline induced hypotension and bradycardia after administration into the area of the nucleus tractus solitarii. Eur J Pharmacol 32:361–363PubMedGoogle Scholar
  136. Nolan PC (1977) The effect of serotonin precursors on the pressor response to intravenous clonidine in conscious rats. Clin Exp Pharmacol Physiol 4:579–583PubMedGoogle Scholar
  137. Oates JA, Gillespie L, Udenfriend S, Sjoerdsma A (1960) Decarboxylase inhibition and blood pressure reduction by a-methyl-3,4-dihydroxy-DL-phenylalanine. Science 131:1890–1891PubMedGoogle Scholar
  138. Olpe H-R, Demiéville H, Baltzer V, Bencze WL, Koella WP, Wolf P, Haas HL (1978) The biological activity of d- and l-baclofen (Lioresal). Eur J Pharmacol 52:133–136PubMedGoogle Scholar
  139. Osborne MW (1976) On the genesis of essential hypotension – the possible role of central nervous system dopaminergic neurons. In: Scriabine A, Sweet C (eds) New antihypertensive drugs. Chronographs of the Physiological Sociey of Philadelphia, vol 2. Spectrum, New York, pp 105–134Google Scholar
  140. Palkovits M, Brownstein M, Saavedra JM (1974) Serotonin content of the brainstem nuclei in the rat. Brain Res 80:237–249PubMedGoogle Scholar
  141. Palm D, Langeneckert W, Holtz P (1967) Bedeutung der N- und α-Methylierung für die Affinität von Brenzcatechinaminen zu den adrenergischen Receptoren. Naunyn Schmiedebergs Arch Pharmacol Exp Pathol 258:128–149Google Scholar
  142. Persson B (1980a) Cardiovascular effects of intracerebroventricular GABA, glycine and muscimol in the rat. Naunyn Schmiedebergs Arch Pharmacol 313:225–236PubMedGoogle Scholar
  143. Persson B (1980b) GABA-ergic mechanisms in blood pressure control A pharmacologic analysis in the rat. Acta Physiol Scand [Suppl] 491:1–54Google Scholar
  144. Philippu A, Demmeler R, Roensberg G (1974) Effects of centrally applied drugs on pressor responses to hypothalamic stimulation. Naunyn Schmiedebergs Arch Pharmacol 282:389–400PubMedGoogle Scholar
  145. Pinder RM, Brogden RN, Sawyer PR, Speight TM, Avery GS (1975) Fenfluramine: A review of its pharmacological properties and therapeutic efficacy in obesity. Drugs 10:241–323PubMedGoogle Scholar
  146. Rapport MM (1949) Serum vasoconstrictor (serotonin). V. The presence of Creatinin in the complex: A proposed study of the vasocontrictor principle. J Biol Chem 180:961–969PubMedGoogle Scholar
  147. Roberts E, Frankel S (1950) γ-aminobutyric acid in brain. Fed Proc 9:219Google Scholar
  148. Roberts E, Krause DM (1982) γ-aminobutyric acid system in cardiovascular and cerebrovascular function. Israel J Med Sci 18:75–81PubMedGoogle Scholar
  149. Robson RD, Kaplan HR (1969) An involvement of St 155 [2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride, Catapres] in cholinergic mechanisms. Eur J Pharmacol 5:328–337PubMedGoogle Scholar
  150. Robson RD, Kaplan HR, Laforce S (1969) An investigation into the bradycardic effects of St 155 [2-(2,6-dichlorophenylamino)-2-imidazoline HCl] in the anesthetized dog. J Pharmacol Exp Ther 169:120–131PubMedGoogle Scholar
  151. Saavedra JM, Palkovits M, Browstein MJ, Axelrod J (1974) Localization of phenyl-ethanolamine n-methyl transferase in the rat brain nuclei. Nature 248:695–696PubMedGoogle Scholar
  152. Sattler RW, van Zwieten PA (1967) Acute hypotensive action of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155) after infusion into the cat’s vertebral artery. Eur J Pharmacol 2:9–13PubMedGoogle Scholar
  153. Scatton B, Pelayo F, Dubocovich ML, Langer SZ, Bartholini(1979) Effect of clonidine on utilization and potassium-evoked release of adrenaline in rat brain areas. Brain Res 176:197–201Google Scholar
  154. Schieken RM (1979) The effect of diazepam upon the development of hypertension in the spontaneously hypertensive rat. Pediat Res 13:992–996PubMedGoogle Scholar
  155. Schmitt H, Schmitt H (1969) Localization of the hypotensive effect of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155, Catapresan). Eur J Pharmacol 6:8–12PubMedGoogle Scholar
  156. Schmitt H, Schmitt H (1970) Interactions between 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155, Catapresan) and a-adrenergic blocking drugs. Eur J Pharmacol 9:7–13PubMedGoogle Scholar
  157. Schmitt H, Schmitt H, Boissier JR, Giudicelli JF (1967) Centrally mediated decrease in sympathetic tone induced by 2-(2,6-dichlorophenylamino)-2-imidazoline (St 155, Catapresan). Eur J Pharmacol 2:147–148PubMedGoogle Scholar
  158. Schmitt H, Schmitt H, Boissier JR, Giudicelli JF, Fichelle J (1968) Cardiovascular effects of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155). II. Central sympathetic structures. Eur J Pharmacol 2:340–346PubMedGoogle Scholar
  159. Schmitt H, Fénard S, Schmitt H (1971a) Influence d’agents bloquants sur les effects inhibiteurs exercés par la clonidine sur les centres vasomoteurs. J Pharmacol (Paris) 2:369–273Google Scholar
  160. Schmitt H, Schmitt H, Fénard S (1971b) Evidence for an a-sympathomimetic component in the effects of Catapresan on vasomotor centers. Antagonism by piperoxane. Eur J Pharmacol 14:98–100PubMedGoogle Scholar
  161. Schneider E, Felix W (1983) The influence of ketanserin on central cardiovascular regulation. Naunyn Schmiedebergs Arch Pharmacol 322:R42Google Scholar
  162. Shaw J, Hunyor SN, Korner PI (1971) Sites of central nervous action of clonidine on reflex autonomic function in the unanaesthetized rabbit. Eur J Pharmacol 15:66–78PubMedGoogle Scholar
  163. Sherman GP, Grega G J, Woods RJ, Buckley JP (1968) Evidence for a central hypotensive mechanism of 2-(2,6-dichlorphenylamino)-2-imidazoline (Catapresan, St 155). Eur J Pharmacol 2:326–328PubMedGoogle Scholar
  164. Sinha JN, Atkinson JM, Schmitt H (1973) Effects of clonidine and L-DOPA on spontaneous and evoked splanchnic nerve discharges. Eur J Pharmacol 24:113–119PubMedGoogle Scholar
  165. Sinha JN, Tangsi KK, Bhargava KP, Schmitt H (1975) Central sites of sympathoinhibitory effects of clonidine and L-DOPA. In: Milliez P, Safar M (eds) Recent advances in hypertension, vol 1. Société Aliéna, Reims, pp 97–109Google Scholar
  166. Sjoerdsma A (1967) Catecholamines and the drug therapy. Circ Res 21 [Suppl III] 21:119–125Google Scholar
  167. Smits JF, Struyker-Boudier HA (1976) Intrahypothalamic serotonin and cardiovascular control in rats. Brain Res 111:422–427PubMedGoogle Scholar
  168. Snead OC (1977) Gamma-hydroxybutyrate. Life Sci 20:1935–1944PubMedGoogle Scholar
  169. Snyder SH (1976) Catecholamines, serotonin, and histamin. In: Siegel GJ, Albers RW, Katzman R, Agranoff BW (eds) Basic neurochemistry, pp 203–217Google Scholar
  170. Soubrie P, Montastruc JC, Bourgoin S, Reisine T, Artaud F, Glowinski J (1981) In vivo evidence for GABAergic control of serotonin release in the cat substantia nigra. Eur J Pharmacol 69:483–488PubMedGoogle Scholar
  171. Sowers JR, Gollub MS, Berger ME, Whitfield LA (1982) Dopaminergic modulation of pressor and hormonal responses in essential hypertension. Hypertension 4:424–430PubMedGoogle Scholar
  172. Starke K, Montel H (1973) Involvement of α-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurones. Neuropharmacology 12: 1073–1080PubMedGoogle Scholar
  173. Starke K, Tanak, Stamm G (1980) Evidence against agonist- and antagonist-selective α-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol 311:R58Google Scholar
  174. Struyker-Boudier HAJ, van Essen H (1982) Hemodynamic actions of ketanserin and the alpha-adrenoceptor blockers prazosin and phentolamine in the conscious SHR. Naunyn Schmiedebergs Arch Pharmacol 322:R42Google Scholar
  175. Struyker-Boudier H, Smeets G, Brouwer G, Rossum J van (1975) Localization of central noradrenergic mechanisms in cardiovascular regulation in rats. Clin Sci 48: 277s-278sGoogle Scholar
  176. Stumpe KO, Higuchi M, Kolloch R, Krück F, Vetter H (1977) Hyperprolactinaemia and antihypertensive effect of bromocriptine in essential hypertension. The Lancet 30:211–214Google Scholar
  177. Svensson TH, Bunney BS, Aghajanian GK (1975) Inhibition of both noradrenergic and serotonergic neurons in brain by the a-adrenergic agonist clonidine. Brain Res 92:291–306PubMedGoogle Scholar
  178. Tadepalli AS, Mills E, Schanberg SM (1977) Central depression of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: Influence of supracollicular areas of the brain. J Pharmacol Exp Ther 202:310–319PubMedGoogle Scholar
  179. Takahashi H, Tiba M, Ino M, Takayasu T (1955) The effect of α-aminobutyric acid on blood pressure. Jpn J Physiol 5:334–339PubMedGoogle Scholar
  180. Takahashi H, Tiba M, Yamazaki T, Noguchi F (1958) On the site of action of γ-aminobutyric acid on blood pressure. Jpn J Physiol 8:378–390PubMedGoogle Scholar
  181. Tappaz M, Brownstein MJ, Kopin IJ (1977) Glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in discrete nuclei of hypothalamus and substantia nigra. Brain Res 125:109–121PubMedGoogle Scholar
  182. Toda N, Fukuda N, Shimamoto K (1969) The mode of hypotensive actions of 2-(2,6-dichlorophenyl-l-amino)-imidazoline in the rabbit. Jpn J Pharmacol 19:199–210PubMedGoogle Scholar
  183. Trolin G (1975) Effects of pentobarbitone and decerebration on the clonidine-induced circulatory changes. Eur J Pharmacol 34:1–7PubMedGoogle Scholar
  184. Tuomilehto J, Siltanen H, Jespersen S (1977) A study on the effect of fenfluramine in obese, hypertensive patients treated with β-adrenergic blocking agents. Curr Ther Res 22:821–827Google Scholar
  185. Twarog BM, Page IH (1953) Serotonin content of some mammalian tissue and urine and a method for its determination. Am J Physiol 175:157–161PubMedGoogle Scholar
  186. Unger Th, Bles F, Ganten D, Lang RE, Rettig R, Schwab NA (1983) GABA-ergic stimulation inhibits central actions of angiotensin II: Pressor responses, drinking, and release of vasopressin. Eur J Pharmacol 90:1–9PubMedGoogle Scholar
  187. U’Prichard DC, Snyder SH (1978) 3 H-catecholamine binding to α-receptor in rat brain: enhancement by reserpine. Eur J Pharmacol 51:145–155PubMedGoogle Scholar
  188. van Nueten JM, Janssen PAJ, van Beek J, Xhonneux R, Verbeuren TJ, Vanhoutte PM (1981) Vascular effects of ketanserin (R41 468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther 218:217–230PubMedGoogle Scholar
  189. van Zwieten PA (1980) Characterization of the central α-adrenoceptors involved in the hypotensive action of clonidine by yohimbine, corynanthine and rauwolscine. Naunyn Schmiedebergs Arch Pharmacol 311:R58Google Scholar
  190. Vickers MD (1969) Gamma-hydroxybutyric acid. Int Anaesthesiol Clin 7:75–89Google Scholar
  191. von Euler V (1946) A specific sympathomimetic ergone in adrenergic nerve fibres (sympathica) and its relation to adrenaline and noradrenaline. Acta Physiol Scand 12:73–97Google Scholar
  192. Warnke E, Hoefke W (1977) Influence of central pretreatment with 6-hydroxydopamine on the hypotensive effect of clonidine. Arzneim Forsch 27:2311–2313Google Scholar
  193. Waszczak BL, Hruska RE, Walters JR (1980) GABA-ergic actions of THIP in vivo and in vitro: a comparison with muscimol and GABA. Eur J Pharmacol 65:21–29PubMedGoogle Scholar
  194. Williford DJ, Hamilton BL, Souza JD, Williams TP, DiMicco J A, Güls RA (1980) Central nervous system mechanisms involving GABA influence arterial pressure and heart rate in the cat. Circ Res 47(l):80–88PubMedGoogle Scholar
  195. Wing LMH, Chalmers JP (1974) Effects of p-chlorophenylalanine on blood pressure and heart rate in normal rabbits with neurogenic hypertension. Clin Exp Pharmacol Physiol 1:219–229PubMedGoogle Scholar
  196. Yen TJ, Stamm NB, Clemens JA (1979) Pergolide: a potent dopaminergic antihypertensive. Life Sci 25:209–216PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York 1983

Authors and Affiliations

  • W. Hoefke
  • W. Gaida
    • 1
  1. 1.Department of PharmacologyBoehringer Ingelheim KGIngelheim am RheinFederal Republic of Germany

Personalised recommendations