Advertisement

Regulation of the Arterial Blood Pressure

  • A. Philippu
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 54 / 1)

Abstract

In recent years impressive work has been carried out concerning the central sites of action of antihypertensive drugs; together with physiologic and histochemical approaches, this work has led to exploration of centres and pathways of the brain involved in the regulation of the arterial blood pressure. The aim of this chapter is to outline recent concepts concerning the importance of catecholamine systems in cardiovascular control. For this purpose attention will on the one hand be focused on experimental hypertension and on the putative role of adrenaline-containing neurones of the brain for blood pressure control and on the other hand on the possible involvement of catecholamine systems in the aetiology of hypertension.

Keywords

Arterial Blood Pressure Pressor Response Hypotensive Effect Nucleus Tractus Solitarii Posterior Hypothalamus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alexander, R.S.: Tonic and reflex function of medullary sympathetic cardiovascular centers. J. Neurophysiol. 9, 205–217 (1946)PubMedGoogle Scholar
  2. Andén, N.-E.: Selective stimulation of central α-autoreceptors following treatment with α- methyldopa and FLA 136. Naunyn-Schmiedebergs Arch. Pharmacol. 306, 263–266 (1979)Google Scholar
  3. Andén, N.-E., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 9, 513–523 (1970)PubMedCrossRefGoogle Scholar
  4. Andén, N.-E., Strömbom, U.: Stimulation of central adrenergic alpha-receptors by L-dopa, alpha-methyldopa and clonidine. In: Central action of drugs in blood pressure regulation. Davies, D.S., Reid, J.L. (eds.), pp. 225–236. Tunbridge Wells: Pitman Medical 1975Google Scholar
  5. Andén, N.-E., Bédard, P., Fuxe, K., Ungerstedt, U.: Early and selective increase in brain dopamine levels after axotomy. Experientia 28, 300–301 (1972)PubMedCrossRefGoogle Scholar
  6. Andén, N.-E., Dahlström, A., Fuxe, K., Larsson, K., Olson, L., Ungerstedt, U.: Ascending monoamine neurons to the telencephalon and diencephalon. Acta Physiol. Scand. 67, 313–326 (1966)CrossRefGoogle Scholar
  7. Andén, N.-E., Grabowska, M., Strömbom, U.: Different alpha-adrenoceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedebergs Arch. Pharmacol. 292, 43–52 (1976)Google Scholar
  8. Antonaccio, M.J., Halley, J.: Clonidine hypotension: lack of effect of bilateral lesions of the nucleus solitarii tract in anaesthetized cats. Neuropharmacol. 16, 431–433 (1977)CrossRefGoogle Scholar
  9. Antonaccio, M.J., Kerwin, L.: Centrally mediated increased reflex vagal bradycardia after L-dopa in monoamine oxidase-inhibited anesthetized dogs. J. Pharmacol. Exp. Ther. 196, 380–388 (1976)PubMedGoogle Scholar
  10. Antonaccio, M.J., Robson, R.D.: The effect of clonidine on adrenergic nerve function in vagotomized and nonvagotomized animals. J. Pharmacol. Exp. Ther. 184, 631–640 (1973)PubMedGoogle Scholar
  11. Antonaccio, M.J., Robson, R.D.: An analysis of the peripheral effects of L-dopa on autonomic nerve function. Br. J. Pharmacol. 52, 41–50 (1974)PubMedGoogle Scholar
  12. Antonaccio, M.J., Robson, R.D., Burrell, R.: The effects of L-dopa and α-methyl-dopa on reflexes and sympathetic nerve function. Eur. J. Pharmacol. 25, 9–18 (1974)PubMedCrossRefGoogle Scholar
  13. Axelrod, J.: Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. Pharmacol. Rev. 18, 95–113 (1966)PubMedGoogle Scholar
  14. Bard, P.: Anatomical organization of central nervous system in relation to control of the heart and blood vessels. Physiol. Rev. 40, [Suppl. 4], 3–26 (1960)Google Scholar
  15. Barrett, A.M.: A comparison of the effects of (dl)-propranolol and (d-propranolol in anaesthetized dogs; beta-receptor blocking and hemodynamic action. J. Pharm. Pharmacol. 21, 241–247 (1969)PubMedCrossRefGoogle Scholar
  16. Baum, T., Shropshire, A.T., Varner, L.L.: Contribution of the central nervous system to the action of several antihypertensive agents (methyldopa, hydralazine and guanethidine). J. Pharmacol. Exp. Ther. 182, 135–144 (1972)PubMedGoogle Scholar
  17. Bhargava, K.P., Mishra, N., Tangri, K.K.: An analysis of central adrenoceptor for control of cardiovascular function. Brit. J. Pharmacol. 45, 596–602 (1972)Google Scholar
  18. Bolme, P., Fuxe, K.: Pharmacological studies on the hypotensive effects of clonidine. Eur. J. Pharmacol. 13, 168–174 (1971)PubMedCrossRefGoogle Scholar
  19. Bolme, P., Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Goldstein, M.: 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, 89–94 (1974)PubMedCrossRefGoogle Scholar
  20. Bousquet, P., Guertzenstein, P.G.: Localization of the central cardiovascular action of clonidine. Br. J. Pharmacol. 49, 573–579 (1973)PubMedGoogle Scholar
  21. Bousquet, P., Feldmann, J., Velly, J., Bloch, R.: Role of the ventral surface of the brain stem in the hypotensive action of clonidine. Eur. J. Pharmacol. 34, 151–156 (1975)PubMedCrossRefGoogle Scholar
  22. Brezenoff, H.E., Jenden, D.J.: Modification of arterial blood pressure in rats following microinjection of drugs into the posterior hypothalamus. Int. J. Neuropharmacol. 8, 593–600 (1969)PubMedCrossRefGoogle Scholar
  23. Briant, R.H., Reid, J.L., Dollery, C.T.: Interaction between clonidine and desipramine in man. Br. Med. J. 1973/I, 522–526Google Scholar
  24. Butcher, L.L., Eastgate, S.M., Hodge, G.K.: Evidence that punctate intracerebral administration of 6-hydroxydopamine fails to produce selective neuronal degeneration. Naunyn- Schmiedebergs Arch. Pharmacol. 285, 31–70 (1974)Google Scholar
  25. Calaresu, F.R., Pearce, J.W.: Effects on heart rate of electrical stimulation of medullary vagal structures in the cat. J. Physiol. (Lond.) 176, 241–251 (1965)Google Scholar
  26. Chalmers, J.P., Reid, J.L.: Participation of central noradrenergic neurons in arterial baroreceptor reflexes in the rabbit. Circ. Res. 31, 789–804 (1972)PubMedGoogle Scholar
  27. Chalmers, J.P., Wurtman, R.J.: Participation of central noradrenergic neurons in arterial baroreceptor reflexes in the rabbit. Circ. Res. 28, 480–491 (1971)PubMedGoogle Scholar
  28. Conway, E.L., Lang, W.J.: Cardiovascular responses produced by the injection of isoprenaline into the cerebral ventricles of the unanaesthetized dog. Clin. exp. Pharmacol. Physiol. 1, 59–64 (1974)CrossRefGoogle Scholar
  29. Cottle, M.K.: Degeneration studies of primary afferents of IX th and X th cranial nerves in the cat. J. Comp. Neurol. 122, 329–345 (1964)PubMedCrossRefGoogle Scholar
  30. Crill, W.E., Reise, D.J.: Distribution of carotid sinus and depressor nerves in the cat brain stem. Am. J. Physiol. 214, 269–276 (1968)PubMedGoogle Scholar
  31. McCubbin, J.W., Kaneko, Y., Page, I.H.: Ability of serotonin and norepinephrine to mimic the central effects of reserpine on vasomotor activity. Circ. Res. 8, 849–858 (1960)PubMedGoogle Scholar
  32. Dahlström, A., Fuxe, K.: 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. 62 [Suppl. 232], 1–55 (1964)Google Scholar
  33. Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta Physiol. Scand. 64 [Suppl. 247], 1–36 (1965)Google Scholar
  34. Day, M.D., Roach, A.G.: Beta-adrenergic receptors in the central nervous system of the cat concerned with control of arterial blood pressure and heart rate. Nature 30–31 (1973)Google Scholar
  35. Day, M.D., Roach, A.G.: Central alpha- and beta-adrenoreceptors modifying arterial blood pressure and heart rate in conscious cats. Br. J. Pharmacol. 51, 325–333 (1974)PubMedGoogle Scholar
  36. Day, M.D., Roach, A.G.: Cardiovascular effects of dopamine after central administration into conscious cats. Br. J. Pharmacol. 58, 505–515 (1976)PubMedGoogle Scholar
  37. Day, M.D., Poyser, R.H., Sempik, J.: Pressor responses to noradrenaline administered into the third cerebral ventricle of anaesthetized and conscious cats. Br. J. Pharmacol. 57, 45P (1976)Google Scholar
  38. de Jong, W.: Noradrenaline: central inhibitory control of blood pressure and heart rate. Eur. J. Pharmacol. 29, 179–181 (1974)PubMedCrossRefGoogle Scholar
  39. de Jong, W., Nijkamp, F.P.: Centrally induced hypotension and bradycardia after administration of alpha-methylnoradrenaline into the area of the nucleus tractus solitarii of the rat. Br. J. Pharmacol. 58, 593–598 (1976)PubMedGoogle Scholar
  40. de Jong, W., Zandberg, P., Bohus, B.: Central inhibitory noradrenergic cardiovascular control. Prog. Brain Res. 42, 285–298 (1975)PubMedCrossRefGoogle Scholar
  41. Dhawan, B.N., Johri, M.B., Singh, G.B., Srimal, R.C., Viswesaram, D.: Effect of clonidine on the excitability of vasomotor loci in the cat. Br. J. Pharmacol. 54, 17–21 (1975)PubMedGoogle Scholar
  42. Dhawan, B.N., Singh, G.B., Srimal, R.C.: The effect of clonidine on some centrally evoked cardiovascular responses. In: Recent advances in hypertension. Milliez, P., Safar, M. (eds.), pp. 111–124. Reims: Société Alinéa 1975Google Scholar
  43. Doba, N., Reis, D.J.: Acute fulminating neurogenic hypertension produced by brainstem lesions in the rat. Circ. Res. 32, 584–593 (1973)PubMedGoogle Scholar
  44. Dollery, C.T., Lewis, P.J., Myers, M.G., Reid, J.L.: Central hypotensive effect of propranolol in the rabbit. Br. J. Pharmacol. 48, 343P (1973)PubMedGoogle Scholar
  45. Dollery, C.T., Reid, J.L.: Central noradrenergic neurons and the cardiovascular actions of clonidine in the rabbit. Br. J. Pharmacol. 47, 206–216 (1973)PubMedGoogle Scholar
  46. Euler, U.S. von: A specific sympathomimetic ergone in adrenergic nerve fibres (sympathin) and its relation to adrenaline and noradrenaline. Acta Physiol. Scand. 12, 73–97 (1946)CrossRefGoogle Scholar
  47. Falck, B., Hillarp, N.A., Thieme, G., Torp, A.: Fluorescence of catecholamines and related compounds with formaldehyde. J. Histochem. Cytochem. 10, 348–354 (1962)CrossRefGoogle Scholar
  48. Fallert, M., Bucher, V.M.: Lokalisation eines blutdruckaktiven Substrats in der Medulla oblongata des Kaninchens. Helv. Physiol. Acta 24, 139–163 (1966)Google Scholar
  49. Farnebo, L.O., Hamberger, B.: Drug-induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta Physiol. Scand. [Suppl. 371], 35–44 (1971)Google Scholar
  50. Feldberg, W., Myers, R.D.: Appearance of 5-hydroxy-tryptamine and an unidentified pharmacologically active lipid acid in effluent from perfused cerebral ventricles. J. Physiol. (Lond.) 184, 837–855 (1956)Google Scholar
  51. Finch, L., Haeusler, G.: Further evidence for a central hypotensive action of alpha-methyldopa in both the rat and cat. Br. J. Pharmacol. 47, 217–228 (1973)PubMedGoogle Scholar
  52. Fitzgerald, J.D.: Perspectives in adrenergic beta-receptor blockade. Clin. Pharmacol. Ther. 10, 292–306 (1969)PubMedGoogle Scholar
  53. Folkow, B., Johansson, B., Öberg, B.: A hypothalamic structure with a marked inhibitory effect on tonic sympathetic activity. Acta Physiol. Scand. 47, 262–270 (1959)Google Scholar
  54. Folkow, B., Langston, J., Öberg, B., Prerovsky, I.: Reactions of the different series-coupled vascular sections upon stimulation of the hypothalamic sympatho-inhibitory area. Acta Physiol. Scand. 61, 476–483 (1964)Google Scholar
  55. Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system: IV. Distribution of monoamine nerve terminals in the central nervous system. Acta Physiol. Scand. 64, [Suppl. 247], 37–85 (1965)Google Scholar
  56. Fuxe, K., Hôkfelt, T., Bolme, P., Goldstein, M., Johansson, O., Jonsson, G., Lidbrink, P., Ljungdahl, A., Sachs, Ch.: The topography of central catecholamine pathways in relation to their possible role in blood pressure control. In: Central action of drugs in blood pressure regulation. Davies, D.S., Reid, J.L. (eds.), pp. 8–23. Tunbridge Wells: Pitman Medical 1975Google Scholar
  57. Gagnon, D.J., Melville, K.I.: Centrally mediated cardiovascular response to isoprenaline. Int. J. Neuropharmacol. 6, 245–251 (1967)PubMedCrossRefGoogle Scholar
  58. Gomes, C., Svensson, T.H., Trolin, G.: Effects of morphine on central catecholamine turnover, blood pressure and heart rate in the rat. Naunyn-Schmiedebergs Arch. Pharmacol. 294, 141–147 (1976a)Google Scholar
  59. Gomes, C., Svensson, T.H., Trolin, G.: Evidence for involvement of central noradrenergic neurons in the cardiovascular depression induced by morphine in the rat. J. Neural Transm. 39, 33–46 (1976 b)PubMedCrossRefGoogle Scholar
  60. Grobecker, H., Saavedra, S.M., Axelrod, J.: Role of central and peripheral catecholaminergic neurones in the development of experimental hypertension. Naunyn-Schmiedebergs Arch. Pharmacol. 297, R 138 (1977)Google Scholar
  61. van der Gugten, J., Palkovits, M., Wijnen, H.L.J.M., Versteeg, D.H.G.: Regional distribution of adrenaline in rat brain. Brain Res. 107, 171–175 (1976)PubMedCrossRefGoogle Scholar
  62. Gupta, P.P., Srimal, R.C., Dhawan, B.N.: Central cardiovascular effects of 6-hydroxydopamine. Eur. J. Pharmacol. 20, 215–223 (1972)PubMedCrossRefGoogle Scholar
  63. Haeusler, G.: Activation of the central pathway of the baroreceptor reflex, a possible mechanism of the hypotensive action of Clonidine. Naunyn-Schmiedebergs Arch. Pharmacol. 278, 231–246 (1973)Google Scholar
  64. Haeusler, G.: Clondine-induced inhibition of sympathetic nerve activity: No indication for a central presynaptic or an indirect sympathomimetic mode of action. Naunyn-Schmiedebergs Arch. Pharmacol. 286, 97–111 (1974)Google Scholar
  65. Haeusler, G.: Cardiovascular regulation by central adrenergic mechanisms and its alteration by hypotensive drugs. Circ. Res. 36., 37, [Suppl. I], I-223–I-232 (1975)Google Scholar
  66. Haeusler, G., Finch, L., Thoenen, H.: Central adrenergic neurones and the initiation and development of experimental hypertension. Experientia 28, 1200–1203 (1972 a)PubMedCrossRefGoogle Scholar
  67. Haeusler, G., Gerold, M., Thoenen, H.: Cardiovascular effects of 6-hydroxydopamine injected into a lateral brain ventricle of the rat. Naunyn-Schmiedebergs Arch. Pharmacol. 274,211–228 (1972 b)PubMedCrossRefGoogle Scholar
  68. Heise, A., Kroneberg, G.: Alpha-sympathetic receptor stimulation in the brain and hypotensive activity of alpha-methyldopa. Eur. J. Pharmacol. 17, 315–317 (1972)PubMedCrossRefGoogle Scholar
  69. Heise, A., Kroneberg, G.: Central nervous alpha-adrenergic receptors and the mode of action of alpha-methyldopa. Naunyn-Schmiedebergs Arch. Pharmacol. 279, 285–300 (1973)Google Scholar
  70. Heller, H.: Über die zentrale Blutdruckwirkung des Adrenalins. Naunyn-Schmiedebergs Arch. Pharmakol. Exp. Pathol. 173, 291–300 (1933)CrossRefGoogle Scholar
  71. Henning, M.: Interaction of dopa decarboxylase inhibitors with the effect of alpha-methyldopa on blood pressure and tissue monoamines in rats. Acta Pharmacol. Toxicol. 27, 1–14 (1969)Google Scholar
  72. Henning, M.: Central action of alpha-methyldopa. In: Central action of drugs in blood pressure regulation. Davies, D.S., Reid, J.L. (eds.), pp. 157–165. Tunbridge Wells: Pitman Medical 1975Google Scholar
  73. Henning, M., Rubenson, A.: Central hypotensive effect of 1-3,4-dihydroxyphenylalanine in the rat. J. Pharm. Pharmacol. 22, 553–560 (1970)PubMedCrossRefGoogle Scholar
  74. Henning, M., Rubenson, A.: Evidence that hypotensive action of alpha-methyldopa is mediated by central actions of alpha-methylnoradrenaline. J. Pharm. Pharmacol. 23, 407–411 (1971).PubMedCrossRefGoogle Scholar
  75. Henning, M., Rubenson, A., Trolin, G.: On the localization of the hypotensive effect of L-dopa. J. Pharm. Pharmacol. 24, 447–451 (1972)PubMedCrossRefGoogle Scholar
  76. Henning, M., Stock, G., Trolin, G.: Circulatory effects of Clonidine after prehypothalamic section in the rat. Acta Pharmacol. Toxicol. 38, 376–381 (1976)Google Scholar
  77. Henning, M., van Zwieten, P.A.: Central hypotensive effect of alpha-methyldopa. J. Pharm. Pharmacol. 19, 403–405 (1967)PubMedCrossRefGoogle Scholar
  78. Henning, M., van Zwieten, P.A.: Central hypotensive effect of alpha-methyldopa. J. Pharm. Pharmacol. 20, 409–417 (1968)PubMedCrossRefGoogle Scholar
  79. Hilliard, C.C., Bagwell, E.E., Daniell, H.B.: Effects of sympathetic and central nervous system alteration on the blood pressure responses to phentolamine. J. Pharmacol. Exp. Ther. 180, 743–747 (1972)PubMedGoogle Scholar
  80. Hilton, S.M.: Ways of viewing the central nervous control of the circulation- old and new. Brain Res. 87, 213–219 (1975)PubMedCrossRefGoogle Scholar
  81. Hilton, S.M., Speyer, K.M.: Participation of the anterior hypothalamus in the baroreceptor reflex. J. Physiol. (Lond.) 218, 271–293 (1971)Google Scholar
  82. Hoefke, W., Kobinger, W.: Pharmakologische Wirkungen des 2-(2,6-Dichlorphenylamino)-2- imidazolin-hydrochlorids, einer neuen, antihypertensiven Substanz. Arzneim. Forsch. 16, 1038–1050 (1966)Google Scholar
  83. Hökfelt, T., Fuxe, K., Goldstein, M., Johansson, O.: Evidence for adrenaline neurons in the rat brain. Acta Physiol. Scand. 89, 286–288 (1973)CrossRefGoogle Scholar
  84. Hökfelt, T., Fuxe, K., Goldstein, M., Johansson, O.: Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain. Brain Res. 66, 235–251 (1974)CrossRefGoogle Scholar
  85. Holmes, R., Newman, P.P., Wolstencroft, J.H.: The distribution of carotic and vertebral blood in the brain of the cat. J. Physiol. (Lond.) 140, 236–246 (1958)Google Scholar
  86. Holtz, P.: Über die sympathomimetische Wirksamkeit von Gehirnextrakten. Acta Physiol. Scand. 20, 354–362 (1950)CrossRefGoogle Scholar
  87. Holtz, P.: Pharmakologie und Biochemie des alpha-Methyldopa. In: Medizinische Klausurgespräche. 2. Therapie des Bluthochdrucks. Heilmeyer, L., Holtmeier, H.J. (eds.), pp. 1–15. Berlin, Freiburg: Verlag für Gesamtmedizin 1963Google Scholar
  88. Holtz, P.: Über den Mechanismus der blutdrucksenkenden Wirkung von alpha-Methyldopa. In: Hochdruckforschung. Fortschritte auf dem Gebiet der Inneren Medizin. II. Symposium in Freiburg (i. Br.). Heilmeyer, L., Holtmeier, H.J. (eds.), pp. 3–12. Stuttgart: Thieme 1965Google Scholar
  89. Hukuhara, T., Otsuka, Y., Takeda, R., Sakai, F.: Die zentralen Wirkungen des 2-(2,6-dichlor- phenylamino)-2-imidazolin-hydrochlorids. Arzneim. Forsch. 18, 1147–1153 (1968)Google Scholar
  90. Ingenito, A.J., Barrett, J.P., Procita, L.: A centrally mediated peripheral effect of alpha-methyldopa. J. Pharmacol. Exp. Ther. 175, 593–599 (1970)PubMedGoogle Scholar
  91. Ito, A., Schanberg, S.M.: Maintenance of tonic vasomotor activity by alpha and beta adrenergic mechanisms in medullary cardiovascular centers. J. Pharmacol. Exp. Ther. 189, 392–404 (1974)PubMedGoogle Scholar
  92. Jaju, B.P., Tangri, K.K., Bhargava, K.P.: Central vasomotor effects of alpha-methyldopa. Can. J. Pharmacol. 44, 687–690 (1966)CrossRefGoogle Scholar
  93. Juskewich, J.C., Robinson, D.S., Whitehorn, D.: Effect of hypothalamic stimulation in spontaneously hypertensive and Wistar-Kyoto rats. Eur. J. Pharmacol. 51, 429–439 (1978)CrossRefGoogle Scholar
  94. Kabat, H., Magoun, H.W., Ranson, S.W.: Electrical stimulation of points in the forebrain and midbrain. Resultant alterations in blood pressure. Arch. Neurol. (Chicago) 34, 931–955 (1935)Google Scholar
  95. Kaneko, Y., McCubbin, J.W., Page, J.H.: Mechanism by which serotonin, norepinephrine and reserpine cause central vasomotor inhibition. Circ. Res. 8, 1228–1234 (1960)PubMedGoogle Scholar
  96. Karplus, J.P., Kreidl, A.: Gehirn und Sympathicus. IV. Mitteilung. Pflügers Arch. Ges. Physiol. 171, 192–200 (1918)CrossRefGoogle Scholar
  97. Karplus, J.P., Kreidl, A.: Gehirn und Sympathicus. VII. Mitteilung. Über Beziehungen der Hypothalamuszentren zu Blutdruck und innerer Sekretion. Pflügers Arch. Ges. Physiol. 215, 667–670 (1927)CrossRefGoogle Scholar
  98. Kelliher, G.J., Buckley, J.P.: Central hypotensive activity of dl- and d-propranolol. J. Pharm. Sci. 59, 1276–1280 (1970)PubMedCrossRefGoogle Scholar
  99. Kerr, F.W.L.: Facial, vagal and glossopharyngeal nerves in the cat. Afferent connections. Arch. Neurol. 6, 264–281 (1962)PubMedGoogle Scholar
  100. Klevans, L.R., Kepner, K., Kovacs, J.L.: Role of forebrain in clonidine-induced supression of cardiovascular responses. Eur. J. Pharmacol. 24, 262–265 (1973)PubMedCrossRefGoogle Scholar
  101. Kobinger, W.: Über den Wirkungsmechanismus einer neuen antihypertensiven Substanz mit Imidazolinstruktur. Naunyn-Schmiedebergs Arch. Pharmak. Exp. Pathol. 258, 48–58 (1967)Google Scholar
  102. Kobinger, W.: Central alpha-adrenergic systems as target for hypotensive drugs. Rev. Physiol. Biochem. Pharmacol. 81, 39–100 (1978)PubMedCrossRefGoogle Scholar
  103. Kobinger, W., Pichler, L.: Evidence for direct alpha-adrenoceptor stimulation of effector neurons in cardiovascular centers by Clonidine. Eur. J. Pharmacol. 27, 151–154 (1974)PubMedCrossRefGoogle Scholar
  104. Kobinger, W., Pichler, L.: The central modulatory effect of Clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline. Eur. J. Pharmacol. 30, 56–62 (1975)PubMedCrossRefGoogle Scholar
  105. Kobinger, W., Pichler, L.: Centrally induced reduction in sympathetic tone - a postsynaptic al- pha-adrenoceptor-stimulating action of imidazolines. Eur. J. Pharmacol. 40, 311–320 (1976)PubMedCrossRefGoogle Scholar
  106. Kobinger, W., Walland, A.: Investigations into the mechanism of the hypotensive effect of 2-(2,6-di-chlorphenylamino)-2-imidazolin-HCl. Eur. J. Pharmacol. 2, 155–162 (1967 a)PubMedCrossRefGoogle Scholar
  107. Kobinger, W., Walland, A.: Kreislaufuntersuchungen mit 2-(2,6-Dichlorphenylamino)-2-imidazolin-Hydrochlorid. Arzneim. Forsch. 17, 292–298 (1967 b)Google Scholar
  108. Kobinger, W., Walland, A.: Involvement of adrenergic receptors in central vagus activity. Eur. J. Pharmacol. 16, 120–122 (1971)PubMedCrossRefGoogle Scholar
  109. Kobinger, W., Walland, A.: Evidence for a central activation of a vagal cardiodepressor reflex by clonidine. Eur. J. Pharmacol. 19, 203–209 (1972 a)PubMedCrossRefGoogle Scholar
  110. Kobinger, W., Walland, A.: Facilitation of vagal reflex bradycardia by an action of clonidine on central alpha-receptors. Eur. J. Pharmacol. 19, 210–217 (1972 b)PubMedCrossRefGoogle Scholar
  111. Kobinger, A., Walland, A.: Modulating effect of central adrenergic neurones on a vagally mediated cardioinhibitory reflex. Eur. J. Pharmacol. 22, 344–350 (1973)PubMedCrossRefGoogle Scholar
  112. Korf, J., Aghajanian, G.K., Roth, R.H.: Stimulation and destruction of the locus coeruleus: Opposite effects on 3-methoxy-4-hydroxyphenylglycol sulfate levels in the rat cerebral cortex. Eur. J. Pharmacol. 21, 305–310 (1973)PubMedCrossRefGoogle Scholar
  113. Koslow, S.H., Schlumpf, M.: Quantitation of adrenaline in rat brain nuclei and areas by mass fragmentography. Nature 251, 530–531 (1974)PubMedCrossRefGoogle Scholar
  114. Lang, W J., Lambert, G.A., Rush, M.L.: The role of the central nervous system in the cardiovascular responses to yohimbine. Arch. Int. Pharmacodyn. 217, 57–67 (1975)PubMedGoogle Scholar
  115. Laubie, M.: Interactions between cholinergic and noradrenergic pathways in central control of blood pressure. In: Recent advances in hypertension. Milliez, P., Safar, M. (eds.), pp. 49–59. Reims: Société Alinéa 1975Google Scholar
  116. Laubie, M., Schmitt, H., Drouillat, M.: Action of clonidine on the baroreceptor pathway and medullary sites mediating vagal bradycardia. Eur. J. Pharmacol. 38, 293–303 (1976)PubMedCrossRefGoogle Scholar
  117. Lewis, P.J., Haeusler, G.: Reduction in sympathetic nervous activity as a mechanism for hypotensive effect of propranolol. Nature 256, 440 (1975)PubMedCrossRefGoogle Scholar
  118. Lipski, J., Przybylski, J., Solnicka, E.: Reduced hypotensive effect of clonidine after lesions of the nucleus tractus solitarii in rats. Eur. J. Pharmacol. 38, 19–22 (1976)PubMedCrossRefGoogle Scholar
  119. Löfving, B.: Cardiovascular adjustments induced from the rostral cingulate gyrus with special reference to sympatho-inhibitory mechanisms. Acta Physiol. Scand. 53 [Suppl. 184], 5–82 (1961)Google Scholar
  120. Mansour, E., Capone, R., Mason, D.T.: The mechanism of morphine-induced peripheral arteriolar dilation. - Central nervous sympatholysis. Am. J. Cardiol. 26, 648 (1970)CrossRefGoogle Scholar
  121. Minsker, D.H., Scriabine, A., Stokes, A.L., Stone, C.A., Torchiana, M.L.: Effects of L-dopa alone and in combination with dopa decarboxylase inhibitors on the arterial blood pressure and heart rate of dogs. Experientia 27, 529 (1971)PubMedCrossRefGoogle Scholar
  122. Miura, M., Reis, D.J.: Termination and secondary projections of carotid sinus nerve in the cat brain stem. Am. J. Physiol. 217, 142–153 (1969)PubMedGoogle Scholar
  123. Morales-Aguilerá, A., Vaughan Williams, E.M.: The effects on cardiac muscle of β-receptor antagonists in relation to their activity as local anaesthetics. Br. J. Pharmacol. 24, 332–338 (1965)Google Scholar
  124. Myers, M.G., Lewis, P.J., Reid, J.L., Dollery, C.T.: Brain concentration of propranolol in relation to hypotensive effect in the rabbit with observations on brain propranolol levels in man. J. Pharmacol. Exp. Ther. 192, 327–335 (1975)PubMedGoogle Scholar
  125. Nagaoka, A., Lovenberg, W.: Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats. Eur. J. Pharmacol. 43, 297–306 (1977)PubMedCrossRefGoogle Scholar
  126. Nakamura, K., Gerold, M., Thoenen, H.: Experimental hypertension of the rat: Reciprocal changes of norepinephrine turnover in heart and brain-stem. Naunyn-Schmiedebergs Arch. Pharmacol. 268, 125–139 (1971a)Google Scholar
  127. Nakamura, K., Gerold, M., Thoenen, H.: Genetically hypertensive rats: relationship between the development of hypertension and the changes in norepinephrine turnover of peripheral and central adrenergic neurones. Naunyn-Schmiedebergs Arch. Pharmacol. 271, 157–169 (1971b)Google Scholar
  128. Nashold, B.S., Mannarino, E., Wunderlich, M.: Pressor-depressor blood pressure responses in the cat after intraventricular injection of drugs. Nature 193, 1297–1298 (1962)PubMedCrossRefGoogle Scholar
  129. Nayler, W.G., Stone, J,: An effect of St 155 (Clonidine), 2-(2,6-dichlorphenylamino)-2-imidazo- line hydrochloride, Catapres on relationship between blood pressure and heart rate in dogs. Eur. J. Pharmacol. 10, 161–167 (1970)PubMedCrossRefGoogle Scholar
  130. Nijkamp, P.P., de Jong, W.: Alpha-methylnoradrenaline induced hypotension and bradycardia after administration into the area of the nucleus tractus solitarii. Eur. J. Pharmacol. 32, 361–364 (1975)Google Scholar
  131. Oberholzer, R.J.H.: Lokalisation einer Schaltstelle für den Depressorreflex in der Medulla oblongata des Kaninchens. Helv. Physiol. Acta 13, 331–353 (1955)Google Scholar
  132. Oberholzer, R.J.H.: Circulatory centers in medulla and midbrain. Physiol. Rev. 40 [Suppl. 4], 179–195 (1960)Google Scholar
  133. Onesti, G., Schwartz, A.B., Kim, K.E., Paz-Martinez, V., Swartz, C.: Antihypertensive effect of Clonidine. Circ. Res. 28 [Suppl. II], II-53–II-69 (1971)Google Scholar
  134. Osborne, M.W., Wenger, J.J., Willems, W.: The cardiovascular pharmacology of L(–)-dopa: Peripheral and central effects. J. Pharmacol. Exp. Ther. 178, 517–528 (1971)PubMedGoogle Scholar
  135. Pendleton, R.G., Kaiser, C., Gessner, G., Finlay, E., Green, A.: Studies on SK&F 7698; an inhibitor of phenylethanolamine N-methyltransferase (PNMT). J. Pharmacol. Exp. Ther. 190, 551–562 (1974)PubMedGoogle Scholar
  136. Philippu, A.: Release of catecholamines from the hypothalamus by drugs and electrical stimulation. In: New aspects of storage and release mechanisms of catecholamines. Schümann, HJ., Kroneberg, G. (eds.), pp. 258–267. Berlin, Heidelberg, New York: Springer 1970Google Scholar
  137. Philippu, A.: Role of central adrenergic receptors in cardiovascular control. In: Proceedings 6 th International Congress of Pharmacology (Helsinki), Vol. 4, pp. 97–107 (1975)Google Scholar
  138. Philippu, A., Kittel, E.: Presence of beta-adrenoreceptors in the hypothalamus; their importance for the pressor response to hypothalamic stimulation. Naunyn-Schmiedebergs Arch. Pharmacol. 297, 219–225 (1977)Google Scholar
  139. Philippu, A., Schartner, P.: Inhibition by locally applied alpha-adrenoceptor blocking drugs of the depressor response to stimulation of the anterior hypothalamus. Naunyn-Schmiede¬bergs Arch. Pharmacol. 295, 1–7 (1976)Google Scholar
  140. Philippu, A., Stroehl, U.: Beta-adrenoreceptors of the posterior hypothalamus. Clin. Exp. Hypertension 1, 25–38 (1978)CrossRefGoogle Scholar
  141. Philippu, A., Dietl, H., Ströhl, U., True, V.T.: Adrenoreceptors of the hypothalamus: their importance for the regulation of the arterial blood pressure. In: Catecholamines: basic and clinical frontiers. Usdin, E., Kopin, I.J., Barchas, J. (eds.), pp. 1428–1430. New York, Oxford, Toronto, Sydney, Frankfurt: Pergamon pressGoogle Scholar
  142. Philippu, A., Heyd, G., Burger, A.: Release of noradrenaline from the hypothalamus in vivo. Eur. J. Pharmacol. 9, 52–58 (1970)PubMedCrossRefGoogle Scholar
  143. Philippu, A., Przuntek, H., Heyd, G., Burger, A.: Central effects of sympathomimetic amines on the blood pressure. Eur. J. Pharmacol. 15, 200–208 (1971)PubMedCrossRefGoogle Scholar
  144. Philippu, A., Roensberg, W., Przuntek, H.: Effects of adrenergic drugs on pressor responses to hypothalamic stimulation. Naunyn-Schmiedebergs Arch. Pharmacol. 278, 373–386 (1973 a)PubMedCrossRefGoogle Scholar
  145. Philippu, A., Przuntek, H., Roensberg, W.: Superfusion of the hypothalamus with gamma- aminobutyric acid. Effect on release of noradrenaline and blood pressure. Naunyn- Schmiedebergs Arch. Pharmacol. 276, 103–118 (1973 b)PubMedCrossRefGoogle Scholar
  146. Philippu, A., Demmeler, R., Roensberg, G.: Effects of centrally applied drugs on pressor responses to hypothalamic stimulation. Naunyn-Schmiedebergs Arch. Pharmacol. 282, 389–400 (1974)Google Scholar
  147. Philippu, A., Kittel, E., Schartner, P.: Hypothalamic action of adrenoreceptor blocking agents. In: Mechanisms and recent advances in therapy of hypertension. Liebau, H., Brod, J. (eds.). Contrib. Nephrol. 8„ pp. 195–199 (1977)Google Scholar
  148. Przuntek, H., Guimaraes, S., Philippu, A.: Importance of adrenergic neurons of the brain for the rise of blood pressure evoked by hypothalamic stimulation. Naunyn-Schmiedebergs Arch. Pharmacol. 271, 311–319 (1971)Google Scholar
  149. Reid, J.L., Lewis, P.J., Myers, M.G., Dollery, C.T.: Cardiovascular effects of intracerebroventricular d-, l- and dl-propranolol in the conscious rabbit. J. Pharmacol. Exp. Ther. 188, 394–399 (1974)PubMedGoogle Scholar
  150. Rhoton, A.L., O’Leary, J.L., Ferguson, J.P.: The trigeminal, facial, vagal and glossopharyngeal nerves in the monkey. Arch. Neurol. 14, 530–540 (1966)PubMedGoogle Scholar
  151. Robson, R.D., Kaplan, H.R.: An involvement of St 155 [2-(2,6-dichlorphenylamino)-2-imi- dazoline hydrochloride, Catapres] in cholinergic mechanisms. Eur. J. Pharmacol. 5, 328–337 (1969)PubMedCrossRefGoogle Scholar
  152. Rubenson, A.: Analysis of the action of m-tyrosine on blood pressure in the conscious rat: evidence for a central hypotensive effect. J. Pharm. Pharmacol. 23, 412–419 (1971a)PubMedCrossRefGoogle Scholar
  153. Rubenson, A.: Further studies on the mechanism of the central hypotensive effect of L-dopa, dl-m-tyrosine and l-alpha-methyl-dopa. J. Pharm. Pharmacol. 23, 228–230 (1971b)PubMedCrossRefGoogle Scholar
  154. Saavedra, J.M., Grobecker, H., Axelrod, J.: Adrenaline-forming enzyme in brain-stem: elevation in genetic and experimental hypertension. Science 191, 483–484 (1976)PubMedCrossRefGoogle Scholar
  155. Saavedra, J.M., Palkovits, M., Brownstein, M.J., Axelrod, J.: Localisation of phenylethanolamine N-methyl transferase in the rat brain nuclei. Nature 248, 695–696 (1974)PubMedCrossRefGoogle Scholar
  156. Sattler, R.W., van Zwieten, P.A.: Acute hypotensive action of 2-(2,6-dichlorphenylamino)-2- imidazoline hydrochloride (St 155) after infusion into the cat’s vertebral artery. Eur. J. Pharmacol. 2, 9–13 (1967)PubMedCrossRefGoogle Scholar
  157. Saxena, P.R., Bhargava, K.P.: The importance of a central adrenergic mechanism in the cardiovascular responses to ouabain. Eur. J. Pharmacol. 31, 332–346 (1975)PubMedCrossRefGoogle Scholar
  158. Schläfke, M., Loeschke, H.H.: Lokalisation eines an der Regulation von Atmung und Kreislauf beteiligten Gebietes an der ventralen Oberfläche der Medulla oblongata durch Kälteblokkade. Pflügers Arch. Ges. Physiol. 297, 201–220 (1967)CrossRefGoogle Scholar
  159. Schmitt, H., Fenard, S.: Effects des substances sympathomimetiques sur les centres vasomoteurs. Arch. Int. Pharmacodyn. 190, 229–240 (1971)PubMedGoogle Scholar
  160. Schmitt, H., Schmitt, H.: Localization of the hypotensive effect of 2-(2,6-dichlorphenylamino)-2-imidazoline hydrochloride (St 155, Catapresan). Eur. J. Pharmacol. 6, 8–12 (1969)PubMedCrossRefGoogle Scholar
  161. Schmitt, H., Schmitt, H., Boissier, J.R., Giudicelli, J.F., Fichelle, 1: Cardiovascular effects of 2-(2,6-dichlorphenylamino)-2-imidazoline hydrochloride (St 155). Eur. J. Pharmacol. 2, 340–346 (1968)PubMedCrossRefGoogle Scholar
  162. Schmitt, H., Schmitt, H., Fénard, S.: Evidence for an alpha-sympathomimetic component in the effects of Catapresan on vasomotor centres: antagonism by piperoxane. Eur. J. Pharmacol. 14, 98–100 (1971)PubMedCrossRefGoogle Scholar
  163. Schmitt, H., Schmitt, H., Fénard, S.: New evidence for an alpha-adrenergic component in the sympathetic centres: Centrally mediated decrease in sympathetic tone by l-dopa and its antagonism by piperoxane and yohimbine. Eur. J. Pharmacol. 17, 293–296 (1972)PubMedCrossRefGoogle Scholar
  164. Seller, H., Illert, M.: The localization of the first synapse in the carotid sinus baroreceptor reflex pathway and its alteration of the afferent input. Pflügers Arch. Ges. Physiol. 306, 1–19 (1969)CrossRefGoogle Scholar
  165. Share, N.N.: “Alpha” and “beta” adrenergic receptors in the medullary vasomotor center of the cat. Arch. Int. Pharmacodyn. 202, 362–373 (1973)PubMedGoogle Scholar
  166. Share, N.N., Melville, K.: Centrally mediated sympathetic cardiovascular responses induced by intraventricular norepinephrine. J. Pharmacol. Exp. Ther. 141, 15–21 (1963)PubMedGoogle Scholar
  167. Shaw, J., Hunyor, S.N., Korner, P.I.: Sites of central nervous action of Clonidine on reflex autonomic function in the unanaesthetized rabbit. Eur. J. Pharmacol. 15, 66–78 (1971)PubMedCrossRefGoogle Scholar
  168. Singh, G.B., Srimal, R.C., Dhawan, B.N.: Inhibition by alpha-methylnoradrenaline of central vasomotor loci in cat. Pharmacol. Res. Commun. 5, 329–336 (1973)CrossRefGoogle Scholar
  169. Sinha, J.N., Atkinson, J.M., Schmitt, H.: Effects of Clonidine and L-dopa on spontaneous and evoked splanchnic nerve discharges. Eur. J. Pharmacol. 24, 113–119 (1973)PubMedCrossRefGoogle Scholar
  170. Sinha, J.N., Schmitt, H.: Central sympatho-inhibitory effects of intracisternal and intravenous administrations of noradrenaline in high doses. Eur. J. Pharmacol. 28, 217–221 (1974)PubMedCrossRefGoogle Scholar
  171. Smookler, H.H., Severs, W.B., Kinnard, W.J., Buckley, J.P.: Centrally mediated cardiovascular effects of angiotensin II. J. Pharmacol, exp. Ther. 153, 485–494 (1966)Google Scholar
  172. Srivastava, R.K., Kulshrestha, V.K., Singh, N., Bhargava, K.P.: Central cardiovascular effects of intracerebroventricular propranolol. Eur. J. Pharmacol. 21, 222–229 (1973)PubMedCrossRefGoogle Scholar
  173. Starke, K.: Influence of alpha-receptor stimulants on noradrenaline release. Naturwissenschaften 58, 420 (1971)PubMedCrossRefGoogle Scholar
  174. Starke, K., Altmann, K.P.: Inhibition of adrenergic neurotransmission by Clonidine: an action on prejunctional alpha-receptors. Int. J. Neuropharmacol. 12, 339–347 (1973)CrossRefGoogle Scholar
  175. Starke, K., Montel, H.: Involvement of alpha-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurones. Int. J. Neuropharmacol. 12, 1073–1080 (1973)CrossRefGoogle Scholar
  176. Stern, S., Hoffman, M., Braun, K.: Cardiovascular responses to carotid and vertebral artery infusion of propranolol. Cardiovasc. Res. 5, 425–430 (1971)PubMedCrossRefGoogle Scholar
  177. Struyker Boudier, H.A.J.: Catecholamine receptors in nervous tissue. The relevance of neuronal catecholamine receptors in the mode of action of dopaminergic and antihypertensive drugs: University of Nijmegen ( Netherlands ): Ph. D. Dissertation 1975Google Scholar
  178. Struyker Boudier, H.A.J., Bekers, A.: Adrenaline-induced cardiovascular changes after intrahypothalamic administration to rats. Eur. J. Pharmacol. 31, 153–155 (1975)CrossRefGoogle Scholar
  179. Struyker Boudier, H.A.J., van Rossum, J.M.: Clonidine-induced cardiovascular effects after stereotaxic application in the hypothalamus of rats. J. Pharm. Pharmacol. 24, 410–411 (1972)Google Scholar
  180. Tauberger, G., Kuhn, P.: Untersuchungen der zentralnervosen sympaticusdampfenden Wirkungen von alpa-Methyl-dopa. Naunyn-Schmiedebergs Arch. Pharmakol. 268, 33–43 (1971)Google Scholar
  181. Toda, N., Matsuda, Y., Shimamoto, K.: Cardiovascular effects of sympathomimetic amines injected into the cerebral ventricles of rabbits. Int. J. Neuropharmacol. 8, 451–462 (1969)PubMedCrossRefGoogle Scholar
  182. Torchiana, M.L., Lotti, V.J., Clark, C.M., Stone, C.A.: Comparison of centrally mediated hypotensive action of methyldopa and dopa in cats. Arch. Int. Pharmacodyn. 205, 103–113 (1973)PubMedGoogle Scholar
  183. Trolin, G.G.: Involvement of alpha-adrenergic receptors at different levels of the central nervous system in the regulation of blood pressure and heart frequency. Acta Physiol. Scand. [Suppl. 430] (1975 a)Google Scholar
  184. Trolin, G.G.: Effects of pentobarbitone and decerebration of the clonidine-induced circulatory changes. Eur. J. Pharmacol. 34, (1975 b)Google Scholar
  185. Ungerstedt, U.: Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol. Scand. [Suppl. 367] (1971)Google Scholar
  186. van Zwieten, P.A.: The central action of antihypertensive drugs mediated via central alpha-receptors. J. Pharm. Pharmacol. 25, 89–95 (1973)PubMedGoogle Scholar
  187. van Zwieten, P.A., Pauer, M., van Spanning, H.W., de Langen, C: Interaction between centrally acting hypotensive drugs and tricyclic antidepressants. Arch. Int. Pharmacodyn. 214, 12–30 (1975)PubMedGoogle Scholar
  188. Versteeg, D.H.G., Palkovits, M., van der Gugten, J., Wijnen, H.L.J.M., Smeets, G.W.M., de Jong, W.: Catecholamine content of individual brain regions of spontaneously hypertensive rats (SH-rats). Brain Res. 112, 429–434 (1976)PubMedCrossRefGoogle Scholar
  189. Vogt, M.: The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J. Physiol. (Lond.) 123, 451–481 (1954)Google Scholar
  190. Vollmer, R.R., Buckley, J.P.: Central cardiovascular effects of phentolamine in chloralose anesthetized cats. Eur. J. Pharmacol. 43, 17–25 (1977)PubMedCrossRefGoogle Scholar
  191. Watanabe, A.M., Chase, T.N., Cardon, P.V.: Effect of L-dopa alone and in combination with an extracerebral decarboxylase inhibitor on blood pressure and some cardiovascular reflexes. Clin. Pharmacol. Ther. 11, 740–746 (1970)PubMedGoogle Scholar
  192. Watanabe, A.M., Judy, W.V., Cardon, P.V.: Effect of L-dopa on blood pressure and sympathetic nerve activity after decarboxylase inhibition in cats. J. Pharmacol. Exp. Ther. 188, 107–113 (1974)PubMedGoogle Scholar
  193. Watanabe, A.M., Parks, L.C., Kopin, L.J.: Modification of the cardiovascular effects of L-dopa by decarboxylase inhibitors. J. Clin. Invest. 50, 1322–1328 (1971)PubMedCrossRefGoogle Scholar
  194. Yamabe, H., de Jong, W., Lovenberg, W.: Further studies on catecholamine synthesis in the spontaneously hypertensive rat: Catecholamine synthesis in the central nervous system. Eur. J. Pharmacol. 22, 91–98 (1973)Google Scholar
  195. Yamori, Y., de Yong, W., Yamabe, H., Lovenberg, W., Sjoerdsma, A.: Effects of L-dopa and inhibitors of decarboxylase and monoamine oxidase on brain noradrenaline levels and blood pressure in spontaneously hypertensive rats. J. Pharm. Pharmacol. 24, 690–695 (1972)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1980

Authors and Affiliations

  • A. Philippu

There are no affiliations available

Personalised recommendations