Skip to main content
SpringerLink
Log in

γ-Aminobutyric acid and cardiovascular function

  • Full Papers
  • Published:
Experientia Aims and scope Submit manuscript

Summary

Evidence supporting the hypothesis that GABA-ergic mechanisms are involved in controlling mammalian cardiovascular function has been reviewed and analyzed. In vivo and in vitro studies with GABA-agonists and GABA-antagonists have revealed that activation of GABA-receptors is involved in the control of blood pressure and heart rate. Further studies conducted with agents that modify central and/or peripheral GABA-ergic systems could lead to the discovery of drugs that might be useful for treating certain cardiovascular disorders in man, such as hypertension and stroke, and should increase our understanding of the pathophysiological bases of such disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anchar, V.S., Welch, K.M.A., Chabi, E., Bartosh, K., and Meyer, J.S., Cerebrospinal fluid gamma-aminobutyric acid in neurologic disease. Neurology26 (1976) 777–780.

    Article  Google Scholar 

  2. Antonaccio, M.J., and Halley, J., Inhibition of centrallyevoked pressor responses by diazepam: Evidence for an exclusively supramedullary action. Neuropharmacology14 (1975) 649–657.

    Article  CAS  PubMed  Google Scholar 

  3. Antonaccio, M.J., Kerwin, L., and Taylor, D.G., Effects of central GABA receptor antagonism on evoked diencephalic cardiovascular responses. Neuropharmacology17 (1978) 597–603.

    Article  CAS  PubMed  Google Scholar 

  4. Antonaccio, M.J., Kerwin, L., and Taylor, D.G., Reductions in blood pressure, heart rate and renal sympathetic nerve discharge in cats after central administration of muscimol, a GABA-agonist. Neuropharmacology17 (1978) 783–791.

    Article  CAS  PubMed  Google Scholar 

  5. Anwar, N., and Mason, D.F.J., Two actions of γ-aminobutyric acid on the responses of the isolated basilar artery from the rabbit. Br. J. Pharmac.75 (1982) 177–181.

    Article  CAS  Google Scholar 

  6. Baum, T., and Becker, F.T., Hypotensive and postural effects of the γ-aminobutyric acid agonist muscimol and of clonidine. J. cardiovasc. Pharmac.4 (1982) 165–169.

    Article  CAS  Google Scholar 

  7. Billingsley, M.L., and Suria, A., Effects of peripherally administered GABA and other amino acids on cardiopulmonary responses in anesthetized rats and dogs. Archs int. Pharmacodyn255 (1982) 131–140.

    CAS  Google Scholar 

  8. Billingsley, M.L., Suria, A., Gilman, L., Shokes, L., and Shahvari, M., Evidence for GABA involvement in the peripheral control of blood pressure and vascular resistance. Brain Res. Bull.5 (1980) suppl. 2, 329–336.

    Article  CAS  Google Scholar 

  9. Bircher, R.P., Chai, C.Y., and Wang, S.C., Effects of hexamethonium and tetraethylammonium on cardiac arrhythmias produced by pentylenetetrazol, picrotoxin and deslanoside in dogs. J. Pharmac. exp. Ther.149 (1965) 91–97.

    CAS  Google Scholar 

  10. Bousquet, P., Feldman, J., Bloch, R., and Schwartz, J., The central hypotensive action of baclofen in the anesthetized cat. Eur. J. Pharmac.76 (1981) 193–201.

    Article  CAS  Google Scholar 

  11. Bousquet, P., Feldman, J., Bloch, R., and Schwartz, J., Evidence for a neuromodulatory role of GABA at the first synapse of the baroreceptor reflex pathway: Effects of GABA derivatives injected into the NTS. Naunyn-Schmiedeberg's Arch. Pharmak.319 (1982) 168–171.

    Article  CAS  Google Scholar 

  12. Bousquet, P., Feldman, J., Bloch, R., and Schwartz, J., Cardiovascular effects of intracerebroventricular injections of baclofen in the conscious rabbit. J. Pharm. Pharmac.34, (1982) 584–585.

    Article  CAS  Google Scholar 

  13. Bowery, N.G., Doble, A., Hill, D.R., Hudson, A.L., Thurnbull, M.J., and Warrington, R.: Structure/activity studies at a baclofen-sensitive, bicuculline-insensitive GABA receptor, in: Amino acid neurotransmitters, pp. 333–341. Eds F.V. DeFeudis and P. Mandel. Raven Press New York 1981.

    Google Scholar 

  14. Bowery, N.G., and Hudson, A.L., γ-Aminobutyric acid reduces the evoked release of [3H]noradrenaline from sympathetic nerve terminals. Br. J. Pharmac.66 (1979) 108P.

    CAS  Google Scholar 

  15. Bowery, N.G., and Hudson, A.L, GABAA and GABAB binding sites on cryostat sections of rat atria. Br. J. Pharmac.78 (1983) 89P.

    Google Scholar 

  16. Brennan, T., Haywood, J.R., and Ticku, M.K., GABA receptor binding in spontaneously hypertensive rats. Fedn Proc.40 (1981) 532.

    Google Scholar 

  17. Chai, C.Y., and Wang, S.C., Cardiovascular actions of diazepam in the cat. J. Pharmac. exp. Ther.154 (1966) 271–280.

    CAS  Google Scholar 

  18. Chahl, L.A., and Walker, B., The effect of baclofen on the cardiovascular system of the rat. Br. J. Pharmac.69 (1980) 631–637.

    Article  CAS  Google Scholar 

  19. Costa, E., Di Chiara, G., and Gessa G., eds, GABA and benzodiazepine receptors. Raven Press, New York 1981.

    Google Scholar 

  20. Cruz-Coke, R. Etiology of essential hypertension. Hypertension3 (1981) II—191-II—194.

    Article  Google Scholar 

  21. DeFeudis, F.V., and Mandel, P., eds, Amino Acid Neurotransmitters. Raven Press, New York (1981).

    Google Scholar 

  22. Dhumal, V.R., Gulati, O.D., and Bhavsar, V.H., Central hypotensive effect of γ-aminobutyric acid in anesthetized dogs. J. Pharm. Pharmac.32 (1980) 724–725.

    Article  CAS  Google Scholar 

  23. DiMicco, J.A., Gale, K., Hamilton, B., and Gillis, R.A., GABA receptor control of parasympathetic outflow to heart: Characterization and brainstem localization. Science204 (1979) 1106–1109.

    Article  CAS  PubMed  Google Scholar 

  24. DiMicco, J.A., and Gillis, R.A., Neuro-cardiovascular effects produced by bicuculline in the cat. J. Pharmac. exp. Ther.210 (1979) 1–6.

    CAS  Google Scholar 

  25. DiMicco, J.A., Hamilton, B.L., and Gillis, R.A., Central nervous system sites involved in the cardiovascular effects of picrotoxin. J. Pharmac. exp. Ther.203 (1977) 64–71.

    CAS  Google Scholar 

  26. Edvinsson, L., and Krause, D.N., Pharmacological characterization of GABA receptors mediating vasodilatation of cerebral arteries in vitro. Brain Res.173 (1979) 89–97.

    Article  CAS  PubMed  Google Scholar 

  27. Edvinsson, L., Larsson, B., and Skarby, T., Effect of the GABA receptor agonist muscimol on regional cerebral blood flow in the rat. Brain Res.185 (1980) 445–448.

    Article  CAS  PubMed  Google Scholar 

  28. Elliott, K.A.C., and Hobbiger, F., Gamma aminobutyric acid: Circulatory and respiratory effects in different species; re-investigation of the anti-strychnine action in mice. J. Physiol., Lond.146 (1959) 70–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ferkany, J.W., Butler, I.J., and Enna, S.J. Effect of drugs on rat brain, cerebrospinal fluid and blood GABA content. J. Neurochem.33 (1979) 29–33.

    Article  CAS  PubMed  Google Scholar 

  30. Fujiwara, M., Muramatsu, I., and Shibata, S., γ-Aminobutyric acid receptor on vascular smooth muscle of dog cerebral arteries, Br. J. Pharmac.55 (1975) 561–562.

    Article  CAS  Google Scholar 

  31. Gale, K., Hamilton, B.L., Brown, S.C., Norman W.P., Souza, J.D., and Gillis, R.A., GABA and specific GABA binding sites in brain nuclei associated with vagal outflow. Brain Res. Bull.5 (1980) suppl. 2, 325–328.

    Article  CAS  Google Scholar 

  32. Gillis, R.A., Williford, D.J., Dias Souza, J., and Quest, J.A., Central cardiovascular effects produced by the GABA receptor agonist drug, THIP. Neuropharmacology21 (1982) 545–547.

    Article  CAS  PubMed  Google Scholar 

  33. Guertzenstein, P.G., Blood pressure effects obtained by drugs applied to the ventral surface of the brain stem, J. Physiol., Lond.229 (1973), 395–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ikram, H., Rubin, A.P., and Jewkes, R.F., Effect of diazepam on myocardial blood flow of patients with and without coronary artery disease. Br. Heart J.35 (1973) 626–630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kato, E., Morita, K., Kuba, K., Yamada, S., Kuhara, T., Shinka, T., and Matsumoto, I., Does γ-aminobutyric acid in blood control transmitter release in bullfrog sympathetic ganglia. Brain Res.195 (1980) 208–214.

    Article  CAS  PubMed  Google Scholar 

  36. Krause, D.N., Roberts, E., Wong, E., Degener, P., and Rogers, K., Specific cerebrovascular localization of GABA-related receptors and enzymes. Brain Res. Bull.5 (1980) suppl. 2, 173–177.

    Article  CAS  Google Scholar 

  37. Krause, D.N., Wong, E., Degener, P., and Roberts, E., GABA receptors in bovine cerebral blood vessels: Binding studies with [3]muscimol. Brain Res.185, (1980) 51–57.

    Article  CAS  PubMed  Google Scholar 

  38. Krogsgaard-Larsen, P., Scheel-Krüger, J., and Kofod, H., eds, GABA-neurotransmitters; pharmacochemical, biochemical and pharmacological aspects. Munksgaard Copenhagen 1979.

    Google Scholar 

  39. Kuriyama, K., Haber, B., and Roberts, E., Occurrence of a new L-glutamic acid decarboxylase in several blood vessels of the rabbit, Brain Res.23 (1970) 121–123.

    Article  CAS  PubMed  Google Scholar 

  40. Lalley, P.M., Baclofen: Unexpected disinhibitory effects of Lioresal on cardiovascular and respiratory neurones. Brain Res. Bull.5 (1980) suppl. 2, 565–573.

    Article  CAS  Google Scholar 

  41. Lalley P.M., Inhibition of depressor cardiovascular reflexes by a derivative of γ-aminobutyric acid (GABA) and by general anesthetics with suspected GABA-mimetic effects. J. Pharmac. exp. Ther.215 (1980) 418–425.

    CAS  Google Scholar 

  42. Loscher, W., Cardiovascular effects of GABA, GABA-aminotransferase inhibitors and valproic acid following systemic administration in rats, cats and dogs: Pharmacological approach to localize the site of action. Archs int. Pharmacodyn.257 (1982) 32–58.

    CAS  Google Scholar 

  43. Mirzoyan, S.A., and Akopyan, V.P., The effect produced by gamma-aminobutyric acid on the cerebral circulation and oxygen tension in the brain Farmak. Toksik.5 (1967) 572–574.

    Google Scholar 

  44. Mirzoyan, S.A., Kazaran, V.A., and Akopyan, V.P., The glutamic decarboxylase activity in blood vessels of the brain. Dokl. Acad. Nauk USSR190 (1970) 1241–1243.

    CAS  Google Scholar 

  45. Nicoll, R.A., Pentobarbital: Action on frog motoneurones. Brain Res96 (1975) 119–123.

    Article  CAS  PubMed  Google Scholar 

  46. Okada, Y., and Roberts, E., eds, Problems in GABA research: from brain to bacteria, Excerpta Medica, Amsterdam 1982.

    Google Scholar 

  47. Olpe, H.R., Demieville, H., Baltzer, V., Bencze, W.L., Koella, W.P., Wolf, P., and Haas, H.L., The biological activity of d and l-baclofen (Lioresal®). Eur. J. Pharmac.52 (1978) 133–136.

    Article  CAS  Google Scholar 

  48. Otomo, E., Araki, G., Mori, A., and Kurihara, M., Clinical evaluation of GABA in the treatment of cerebrovascular disorders. Arzneimittel-Forsch.31 (1981) 1511–1523.

    CAS  Google Scholar 

  49. Palkovits, M., and Zaborsky, L., Neuroanatomy of central cardiovascular control. Nucleus tractus solitarii: Afferent and efferent neuronal connections in relation to the baroreceptor reflex arc. Prog. Brain Res.47 (1977) 9–34.

    Article  CAS  PubMed  Google Scholar 

  50. Persson, B. A hypertensive response to baclofen in the nucleus tractus solitarii in rats. J. Pharm. Pharmac.33 (1981) 226–231.

    Article  CAS  Google Scholar 

  51. Persson, B., and Henning, M., Central cardiovascular and biochemical effects of baclofen in the conscious rat. J. Pharm. Pharmac.32 (1980) 417–422.

    Article  CAS  Google Scholar 

  52. Persson, B., and Henning, M., Central cardiovascular effect of gamma-hydroxybutyric acid; interactions with noradrenaline, serotonin, dopamine and acetylcholine transmission. Acta pharmac. tox.47 (1980) 135–143.

    Article  CAS  Google Scholar 

  53. de S. Pinto, O., Polikar, M., and DeBono, G., Results of international clinical trials with Lioresal. Post-grad. med. J48 (1972) suppl. 5, 18–23.

    Google Scholar 

  54. Polosa, C., Teare, J.L., and Wyszogrodski, I., Slow rhythms of sympathetic discharge induced by convulsant drugs. Can. J. Physiol. Pharmac.50 (1972) 188–194.

    Article  CAS  Google Scholar 

  55. Porsius, A.J., Lambrecht, G., Moser, U., and Mutschler, E., Depressor effects of isoguvacine propyl ester and isoarecaidine propyl ester due to stimulation of central GABA receptors in the cat. Eur. J. Pharmac.77 (1982) 49–52.

    Article  CAS  Google Scholar 

  56. Roberts, E., and Krause, D.N., γ-Aminobutyric acid system in cardiovascular and cerebrovascular function. Israel J. med. Sci.18 (1982) 75–81.

    CAS  PubMed  Google Scholar 

  57. Rotiroti, D., Palella, B., Losi, E., Nistico, G., and Caputi, P., Evidence that a GABAergic mechanism influences the development of DOCA-salt hypertension in the rat. Eur. J. Pharmac.83 (1982) 153–154.

    Article  CAS  Google Scholar 

  58. Schieken, R.M., The effect of diazepam upon the development of hypertension in the spontaneously hypertensive rat. Pediat Res.13 (1979) 992–996.

    Article  CAS  PubMed  Google Scholar 

  59. Share, N.N., and Melville, K.I., Intraventricular injections of picrotoxin following central adrenergic blockade with phenoxybenzamine and dichloroisoproterenol. Int. J. Neuropharmac. col.4 (1965) 149–156.

    Article  CAS  Google Scholar 

  60. Shibata, N., Shimizu, S., Kubo, M., Takahashi, H., Yamaguchi, Y., Ezoe, T., and Tsukada, Y.: Clinical aspects of the use of gamma-aminobutyric acid, in: Inhibition in the nervous system and γ-aminobutyric acid, p. 579. Eds E. Roberts, C.F. Baxter, A. Van Harrevald, C.A.G. Wiersma, W.R. Adey and K.F. Killam. Pergamon Press, Oxford 1960.

    Google Scholar 

  61. Sigg, E.B., Keim, K.L., and Kepner, K. Selective effect of diazepam on certain central sympathetic centers. Neuropharmacology10 (1971) 621–629.

    Article  CAS  PubMed  Google Scholar 

  62. Snyder, D.W., Macklem, L.J., and Severini, W.H., Central cardiovascular effects of the GABA mimetic agent, THIP. Abstr. 10th Ann. Meet Soc. Neurosci.6 (1980) 755.

    Google Scholar 

  63. Stanovnik, L., Huchet, A.M., and Schmitt, H., The action of baclofen on blood pressure and sympathetic activity, in: 7th Int. Congr. Pharmac. (1978) Abstr. No. 2708.

  64. Stanton, H.C., and Woodhouse, F.H., The effect of gamma-amino-n-butyric acid and some related compounds on the cardiovascular system of anesthetized dogs. J. Pharmac. exp. Ther.128 (1960) 233–242.

    CAS  Google Scholar 

  65. Starke, K., and Weitzell, R., γ-Aminobutyric acid and postganglionic sympathetic transmission in the pulmonary artery of the rabbit. J. Autonom. Pharmac.1 (1980) 45–51.

    Article  CAS  Google Scholar 

  66. Sudakov, K.V., Organization of cardiovascular functions under experimental emotional stress. J. Autonom. Nerv. Syst.4 (1981) 165–180.

    Article  CAS  Google Scholar 

  67. Sweet, C.S., Wenger, H.C., and Gross, D.M., Central antihypertensive properties of muscimol and related γ-aminobutyric acid agonists and the interaction of muscimol with baroreceptor reflexes. Can. J. Physiol. Pharmac.57 (1979) 600–605.

    Article  CAS  Google Scholar 

  68. Takahashi, H., Sumi, M., and Koshino, F., Effect of γ-amino-butyric acid (GABA) on normotensive or hypertensive rats and men. Jap. J. Physiol.11 (1961) 89–95.

    Article  CAS  Google Scholar 

  69. Takahashi, H., Tiba, M., Yamazaki, T., and Noguchi, F., On the site of action of γ-aminobutyric acid on blood pressure. Jap. J. Physiol.8 (1958) 378–390.

    Article  CAS  Google Scholar 

  70. Tallman, J.F., Paul, S.M., Skolnik, P., and Gallager, D.W., Receptors for the age of anxiety: Pharmacology of the benzodiazepines. Science207 (1980) 274–281.

    Article  CAS  PubMed  Google Scholar 

  71. Ticku, M.K., Brennan, T., Burch, T.P., and Thyagarajan, R., GABA and benzodiazepine binding in spontaneously hypertensive rat. Fedn Proc.41 (1982) 1633.

    Google Scholar 

  72. Tunnicliff, G., A relationship between synaptosomal GABA uptake and blood pressure in five inbred strains of mice. Neurochem. Int.4 (1982) 321–327.

    Article  CAS  PubMed  Google Scholar 

  73. Tunnicliff, G., The binding of3H-GABA to synaptic membranes of spontaneously hypertensive rats. Abstr. 12th Ann. Meet. Soc. Neurosci.8 (1982) 561 (Part 2).

    Google Scholar 

  74. van Gelder, N.M., A possible enzyme barrier for γ-aminobutyric acid in the central nervous system, in: Brain barrier systems, progress in brain research, vol. 29, pp. 259–268. Eds A. Lajtha and D. Ford, Elsevier, Amsterdam 1968.

    Chapter  Google Scholar 

  75. Varma, D.R., Share, N.N., and Melville, K.I., Cardiovascular responses following injection of picrotoxin into the lateral cerebral ventricle of rabbits. Int. J. Neuropharmac.1 (1962) 203–206.

    Article  CAS  Google Scholar 

  76. Welch, K.M.A., Chabi, E., Bartosh, K., Anchar, V.S., and Meyer, J.S., Cerebrospinal fluid γ-aminobutyric acid levels in migraine. Br. Med. J.3 (1975) 516–517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. White, H.L., 4-Aminobutyrate: 2-oxoglutarate aminotransferase levels in blood platelets. Science205, (1979) 696–698.

    Article  CAS  PubMed  Google Scholar 

  78. Whitehead, W.E., Blackwell, B., and Robinson, A., Why physicians prescribe benzodiazepines in essential hypertension: A phase IV study. Biol. Psychiat.12 (1977) 597–601.

    CAS  PubMed  Google Scholar 

  79. Williford, D.J., DiMicco, J.A., and Gillis, R.A., Evidence for the presence of a tonically active forebrain GABA system influencing, central sympathetic outflow in the cat. Neuropharmacology19 (1980) 245–250.

    Article  CAS  PubMed  Google Scholar 

  80. Williford, D.J., Hamilton, B.L., Yamada, K., and Gillis, R.A., Evidence that the ventral surface of the brain stem is the site where muscimol acts to produce hypotension and bradycardia. Abstr. 10th Ann. Meet. Soc. Neurosci.6 (1980) 755.

    Google Scholar 

Download references

Author information

Author notes

  1. F. V. DeFeudis (Professeur Conventionné)

    Present address: Université Louis Pasteur, F-67085, Strasbourg Cedex, France

Authors and Affiliations

    Authors
    1. F. V. DeFeudis
      View author publications

      You can also search for this author in PubMed Google Scholar

    Rights and permissions

    Reprints and permissions

    About this article

    Cite this article

    DeFeudis, F.V. γ-Aminobutyric acid and cardiovascular function. Experientia 39, 845–849 (1983). https://doi.org/10.1007/BF01990401

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/BF01990401

    Keywords

    Search

    Navigation