Skip to main content
Log in

Involvement of both GABAA and GABAB receptors in tonic inhibitory control of blood pressure at the rostral ventrolateral medulla of the rat

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The rostral ventrolateral medulla (RVLM) contains vasopressor neurons which increase vasomotor tone. Endogenous GABA is suggested to be involved in mediation of the tonic inhibition of vasopressor neurons in the RVLM. To obtain more precise information about GABAergic mechanisms in the RVLM, we microinjected GABA agonists and antagonists unilaterally into the RVLM and examined their effects on blood pressure and heart rate. In addition, involvement of the other inhibitory amino acids glycine, β-alanine and taurine in blood pressure regulation in the rat RVLM was also investigated. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The GABAA agonist muscimol (3–30 pmol) and the GABAB agonist baclofen (10–100 pmol) microinjected into the RVLM produced a decrease in blood pressure. The GABAA antagonist bicuculline (300 pmol) abolished the depressor response to muscimol (10 pmol) but not to baclofen (30 pmol) whereas the GABAB antagonist 2-hydroxysaclofen (1 nmol) abolished the depressor response to baclofen (30 pmol) but not to muscimol (10 pmol). Either bicuculline or 2-hydroxysaclofen alone produced a pressor response. Both antagonists inhibited depressor response to nipecotic acid (7.7 nmol)and GABA (0.3 nmol). Glycine (0.13 – 4.0 nmol), β-alanine (0.11 – 3.4 nmol) and taurine (0.08 – 2.4 nmol) microinjected into the RVLM also produced decreases in blood pressure. The glycine antagonist strychnine (0.58 nmol) abolished the depressor response to glycine, β-alanine and taurine but not to GABA. The taurine antagonist (6-aminomethyl-3-methyl-4-H-1,2,4-benzothiadiazine-1,1-diox-ide) (1.3 nmol) inhibited the depressor response to β-alanine and taurine but not to glycine and GABA. These results show that in the rat RVLM there exist GABAA and GABAB receptors, and that endogenous GABA tonically stimulates both GABAA and GABAB receptors to decrease arterial pressure. It seems unlikely that glycine and taurine are involved in mediation of the tonic inhibition of vasopressor neurons in the rat RVLM.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Al-Dahan MI, Tehrani MHJ, Thalmann RH (1990) Effect of 2-hydroxysaclofen, an antagonist of GABAB action, upon the binding of baclofen and other receptor ligands in rat cerebrum. Brain Res 526: 308–312

    Google Scholar 

  • Amendt K, Czachurski J, Dembowsky K, Seller H (1979) Bulbospinal projections to the intermediolateral cell column; a neuroanatomical study. J Anton Nerv Syst 1:103–117

    Google Scholar 

  • Bousquet P, Feldman J, Bloch R, Schwartz J (1981) Central cardiovascular effects of taurine: comparison with homotaurine and muscimol. J Pharmacol Exp Ther 219:213–218

    Google Scholar 

  • Bowery N (1989) GABAB receptors and their significance in mammalian pharmacology. Trends Pharmacol Sci 10:401–407

    Google Scholar 

  • Bowery NG, Hudson AL, Price GW (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20:365–383

    Google Scholar 

  • Brown DL, Guyenet PG (1984) Cardiovascular neurons of brain stem with projections to spinal cord. Am J Physiol 247:R1009-R1016

    Google Scholar 

  • Brown DL, Guyenet PG (1985) Electrophysiological study of cardiovascular neurons in the rostral ventrolateral medulla in rats. Circ Res 56:359–369

    Google Scholar 

  • Caverson MM, Ciriello J, Calaresu FR (1983) Cardiovascular afferent inputs to neurons in the ventrolateral medulla projecting directly to the central autonomic area of the thoracic cord in the cat. Brain Res 247:354–358

    Google Scholar 

  • Colmers WF, Williams JT (1988) Pertussis toxin treatment discriminates between pre- and postsynaptic actions of baclofen in rat dorsal raphe nucleus in vitro. Neurosci Lett 93:300–306

    Google Scholar 

  • Curtis DR, Hosli L, Johnston GAR, Johnston IH (1968) The hyperpolarization of spinal motoneurons by glycine and related amino acids. Exp Brain Res 5:235–258

    Google Scholar 

  • Curtis DR, Synther BD, Beatti DT, Kerr DIB, Prager RH (1988) Baclofen antagonism by 2-hydroxy-saclofen in the cat spinal cord. Neurosci Lett 92:97–101

    Google Scholar 

  • Dampney RAL, Blessing WW Tan E (1988) Origin of tonic GABAergic inputs to vasopressor neurons in the subretrofacial nucleus of the rabbit. J Auton Nerv Syst 24:227–239

    Google Scholar 

  • Dampney RAL, Goodchild AK, Robertson LG, Montgomery W (1982) Role of ventrolateral medulla in vasomotor regulation: a correlative anatomical and physiological study. Brain Res 249:223–235

    Google Scholar 

  • DeFeudis FV, Martin Del Rio R (1977) Is β-alanine an inhibitory neurotransmitter? Gen Pharmacol 8:177–180

    Google Scholar 

  • Drew CA, Johnston GAR, Kerr DIB, Ong J (1990) Inhibition of baclofen binding to rat cerebellar membranes by phaclofen, saclofen, 3-aminopropyl-phosphonic acid and related GABAB receptor antagonists. Neurosci Lett 113:107–110

    Google Scholar 

  • Gatti PJ, Souza JP, Namath IJ, Da Silva AMT, Holtman JR Jr., Gillis R (1985) Comparative cardiorespiratory effects produced by taurine and glycine applied to the ventral surface of the medulla. J Pharmacol Exp Ther 235:820–828

    Google Scholar 

  • Harrison NL (1990) On the presynaptic action of baclofen at inhibitory synapses between cultured rat hippocampal neurons. J Physiol 422:433–446

    Google Scholar 

  • Hong Y, Henry JL (1991) Effects of phaclofen and the enantiomers of baclofen on cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat. Eur J Pharmacol 196:267–275

    Google Scholar 

  • Howe JR, Sutor B, Zieglgansberger W (1987) Baclofen reduces postsynaptic potentials of rat cortical neurons by an action other than its hyperpolarizing action. J Physiol 384:539–569

    Google Scholar 

  • Johnston GAR (1986) Multiplicity of GABA receptors. In: Olsen ER, Venter JC (eds) Benzodiazepine/GABA receptors and chloride channels. Receptor biochemistry and methodology, Vol 5. Liss, New York, pp 57–71

    Google Scholar 

  • Johnston GAR, Hailstone MH, Freeman CG (1980) Baclofen: stereoselective inhibition of excitant amino-acid release. J Pharm Pharmacol 32:230–231

    Google Scholar 

  • Johnston GAR, Stephanson AL, Twitchin B (1976) Uptake and release of nipecotic acid by rat brain slices. J Neurochem 26:83–87

    Google Scholar 

  • Keeler JR, Shults CW Chase TN, Helke CJ (1984) The ventral surface of the medulla in the rat: pharmacological autoradiographic localization of GABA-induced cardiovascular effects. Brain Res 297:217–224

    Google Scholar 

  • Kihara M, Kubo T (1989) Immunocytochemical localization of GABA containing neurons in the ventrolateral medulla oblongata of the rat. Histochemistry 91:309–314

    Google Scholar 

  • Kihara M, Amano H, Misu Y, Kubo T (1989) Release of [3H]-and endogenous GABA from slices of the rat medulla oblongata: modification by 3-mercaptopropionic acid, nipecotic acid and diaminobutyric acid. Arch Int Pharmacodyn 298:50–60

    Google Scholar 

  • Kleinman LI, Radford EP (1964) Ventilation standards for small mammals. J Appl Physiol 19:360–362

    Google Scholar 

  • Krogsgaard-Larsen P, Johnston GAR (1975) Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J Neurochem 25:797–802

    Google Scholar 

  • Kubo T, Kihara M (1987) Studies of GABAergic mechanisms responsible for cardiovascular regulation in the rostral ventrolateral medulla of the rat. Arch Int Pharmacodyn 285:277–287

    Google Scholar 

  • Kubo T, Kihara M (1988) N-Methyl-D-aspartate receptors mediate tonic vasodepressor control in the caudal ventrolateral medulla of the rat. Brain Res 451:366–370

    Google Scholar 

  • Kubo T, Kihara M (1991) Modulation of the aortic baroreceptor reflex by neuropeptide Y, neurotensin and vasopressin microinjected into the nucleus tractus solitarii of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 342:182–188

    Google Scholar 

  • Kubo T, Kihara M, Misu Y (1989) Altered amino acid levels in brainstem regions of spontaneously hypertensive rats. Clin Exp Hypertens A11:233–241

    Google Scholar 

  • Kubo T, Nagura J, Kihara M, Misu Y (1986) Cardiovascular effects of L-glutamate and γ-aminobutyric acid injected into the rostral ventrolateral medulla in normotensive and spontaneously hypertensive rats. Arch Int Pharmacodyn 279:150–161

    Google Scholar 

  • Lambert NA, Harrison NL, Kerr DIB, Ong J, Prager RH, Teyler TJ (1989) Blockade of the late IPSP in rat CA1 hippocampal neurons by 2-hydroxy-saclofen. Neurosci Lett 107:125–128

    Google Scholar 

  • Martin GE, Bendesky RJ, Williams M (1981) Further evidence for a selective antagonism of taurine by 6-aminomethyl-4H-1,2,4-benzothiadiazine-1,1-dioxide. Brain Res 229:530–535

    Google Scholar 

  • McCormick DA (1989) GABA as an inhibitory neurotransmitter in human cerebral cortex. J Neurophysiol 62:1018–1027

    Google Scholar 

  • Newberry NR, Nicoll RA (1984) Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308:450–452

    Google Scholar 

  • Potashner SJ (1978) Baclofen: effects on amino acid release. Canad J Physiol Pharmacol 56:150–154

    Google Scholar 

  • Reis DJ, Ross CA, Ruggiero DA, Granata AR, Joh TH (1984) Role of adrenaline neurons of ventrolateral medulla (the Cl group) in the tonic and phasic control of arterial pressure. Clin Exp Hypert A 6:221–241

    Google Scholar 

  • Ross CA, Ruggiero DA, Park DH, Job TH, Sved AF, Fernandez-Pardal J, Saavedra JM, Reis DJ (1984) Tonic vasomotor control by the rostral ventrolateral medulla: effect of electrical or chemical stimulation of the area containing Cl adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin. J Neurosci 4:474–494

    Google Scholar 

  • Seabrook GR, Howson W, Lacey MG (1990) Electrophysiological characterization of potent agonists and antagonists at pre- and postsynaptic GABAB receptors on neurons in rat brain slices. Br J Pharmacol 101:949–957

    Google Scholar 

  • Sivilotti L, Nistri A (1989) Pharmacology of a novel effect of γ-aminobutyric acid on the frog optic tectum in vitro. Eur J Pharmacol 164:205–212

    Google Scholar 

  • Sun M-K, Guyenet PG (1985) GABA-mediated baroreceptor inhibition of reticulo-spinal neurons. Am J Physiol 249:R672-R680

    Google Scholar 

  • Sun M-K, Hackett JT, Guyenet PG (1988) Sympathoexcitatory neurons of rostral ventrolateral medulla exhibit pacemaker properties in the presence of a glutamate-receptor antagonist. Brain Res 438:23–40

    Google Scholar 

  • Sved AF, Sved JC (1990) Endogenous GABA on GABAB receptors in nucleus tractus solitarius to increase blood pressure. Brain Res 526:235–240

    Google Scholar 

  • Urbanski RW, Sapru HN (1988) Putative neurotransmitters involved in medullary cardiovascular regulation: J Auton Nerv Syst 25: 181–193

    Google Scholar 

  • Wessberg P, Hedner T, Hedner J, Jonason J (1983) Effects of taurine and a taurine antagonist on some respiratory and cardiovascular parameters. Life Sci 33:1649–1655

    Google Scholar 

  • Willette RN, Barcas PP, Krieger AJ, Sapru HN (1983a) Vasopressor and depressor areas in the rat medulla. Identification by microinjection of L-glutamate. Neuropharmacology 22:1071–1079

    Google Scholar 

  • Willette RN, Krieger AJ, Barcas PP, Sapru HN (1983b) Medullary γ-aminobutyric acid (GABA) receptors and the regulation of blood pressure in the rat. J Pharmacol Exp Ther 226:893–899

    Google Scholar 

  • Willette RN, Barcas PP, Krieger AJ, Sapru HN (1984) Endogenous GABAergic mechanisms in the medulla and the regulation of blood pressure. J Pharmacol Exp Ther 230:34–39

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correpondence to T Kubo at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amano, M., Kubo, T. Involvement of both GABAA and GABAB receptors in tonic inhibitory control of blood pressure at the rostral ventrolateral medulla of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 348, 146–153 (1993). https://doi.org/10.1007/BF00164791

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00164791

Key words

Navigation