Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Jul;88(3):659–670. doi: 10.1111/j.1476-5381.1986.tb10248.x

Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia.

S Giuliani, C A Maggi, A Meli
PMCID: PMC1916971  PMID: 3742154

Abstract

The cardiovascular (blood pressure, heart rate, cardiac contractility) effects of i.v. gamma-aminobutyric acid (GABA) were investigated in guinea-pigs anaesthetized with barbitone or urethane. GABA (0.1-10 mg kg-1) produced a transient 'depressive' effect on cardiovascular parameters which in barbitone-anaesthetized animals was followed by a transient 'excitatory' effect. Resting cardiovascular parameters were higher in urethane-as compared to barbitone-anaesthetized animals. Picrotoxin pretreatment (2 mg kg-1, i.v.) barely affected the cardiovascular changes produced by GABA in barbitone-anaesthetized animals. In picrotoxin pretreated animals anaesthetized with urethane, GABA produced an initial depression of cardiovascular parameters followed by an excitatory phase. Hexamethonium (20 mg kg-1, i.v.) suppressed or reduced markedly the GABA-induced cardiovascular changes both in barbitone- or urethane- anaesthetized animals. Reserpine pretreatment lowered resting cardiovascular parameters. In these animals, regardless of type of anaesthesia, the effects of i.v. GABA were of the 'excitatory' type only. Reserpine pretreated animals anaesthetized with barbitone were selected for further experiments. Various GABAA receptor agonists (homotaurine, muscimol, THIP, 5-aminovaleric acid) mimicked the 'excitatory' effect of GABA in reserpine pretreated animals anesthetized with barbitone and prevented the effects of subsequent GABA administration. On the other hand (+/-)-baclofen, a selective GABAB receptor agonist, had a slight depressant effect and did not prevent the 'excitatory' cardiovascular effects of GABA. Neither bicuculline nor picrotoxin pretreatment prevented the 'excitatory' cardiovascular effect of i.v. GABA in reserpine pretreated, guinea-pigs anaesthetized with barbitone. In adrenalectomized guinea-pigs or in preparations receiving i.v. phentolamine plus propranolol, GABA produced only a small 'depressant' effect on cardiovascular parameters. These findings demonstrate that GABA exerts a neuromodulatory effect on cardiovascular function via peripheral actions which is influenced by: type of anaesthesia resting values of cardiovascular parameters degree of activity of the sympathetic nervous system and catecholamine release from the adrenal medulla.

Full text

PDF
659

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Advenier C., Boissier J. R., Ho S., Mallard B., Ruff F. The effects of pentobarbitone and urethane on pulmonary airway resistance in guinea-pigs and their interactions with drugs. Br J Pharmacol. 1978 Dec;64(4):519–525. doi: 10.1111/j.1476-5381.1978.tb17313.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anwar N., Mason D. F. Two actions of gamma-aminobutyric acid on the responses of the isolated basilar artery from the rabbit. Br J Pharmacol. 1982 Jan;75(1):177–181. doi: 10.1111/j.1476-5381.1982.tb08770.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bowery N. G., Doble A., Hill D. R., Hudson A. L., Shaw J. S., Turnbull M. J., Warrington R. Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol. 1981 Apr 24;71(1):53–70. doi: 10.1016/0014-2999(81)90386-1. [DOI] [PubMed] [Google Scholar]
  4. Bowery N. G., Hill D. R., Hudson A. L. Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes. Br J Pharmacol. 1983 Jan;78(1):191–206. doi: 10.1111/j.1476-5381.1983.tb09380.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. ELLIOTT K. A., HOBBIGER F. gamma Aminobutyric acid; circulatory and respiratory effects in different species; re-investigation of the anti-strychnine action in mice. J Physiol. 1959 Apr 23;146(1):70–84. doi: 10.1113/jphysiol.1959.sp006178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Giotti A., Luzzi S., Maggi C. A., Spagnesi S., Zilletti L. Modulatory activity of GABAB receptors on cholinergic tone in guinea-pig distal colon. Br J Pharmacol. 1985 Apr;84(4):883–895. doi: 10.1111/j.1476-5381.1985.tb17383.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Giotti A., Luzzi S., Spagnesi S., Zilletti L. GABAA and GABAB receptor-mediated effects in guinea-pig ileum. Br J Pharmacol. 1983 Mar;78(3):469–478. doi: 10.1111/j.1476-5381.1983.tb08807.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hayes J. S. A simple technique for determining contractility, intraventricular pressure, and heart rate in the anesthetized guinea pig. J Pharmacol Methods. 1982 Nov;8(3):231–239. doi: 10.1016/0160-5402(82)90077-8. [DOI] [PubMed] [Google Scholar]
  9. Horvath J. S., Baxter C. R., Duggin G., Tiller D. J. The effect of intravenous administration of GABA and brain extracts on blood pressure in the rat. Clin Exp Pharmacol Physiol. 1980 Sep-Oct;7(5):481–485. doi: 10.1111/j.1440-1681.1980.tb00096.x. [DOI] [PubMed] [Google Scholar]
  10. Kataoka Y., Gutman Y., Guidotti A., Panula P., Wroblewski J., Cosenza-Murphy D., Wu J. Y., Costa E. Intrinsic GABAergic system of adrenal chromaffin cells. Proc Natl Acad Sci U S A. 1984 May;81(10):3218–3222. doi: 10.1073/pnas.81.10.3218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kato E., Kuba K. Inhibition of transmitter release in bullfrog sympathetic ganglia induced by gamma-aminobutyric acid. J Physiol. 1980 Jan;298:271–283. doi: 10.1113/jphysiol.1980.sp013080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kitayama S., Morita K., Dohi T., Tsujimoto A. The nature of the stimulatory action of gamma-aminobutyric acid in the isolated perfused dog adrenals. Naunyn Schmiedebergs Arch Pharmacol. 1984 Jun;326(2):106–110. doi: 10.1007/BF00517305. [DOI] [PubMed] [Google Scholar]
  13. Kushiku K., Furukawa T. Possible inhibitory role of endogenous gamma-aminobutyric acid in the nonnicotinic functions of the dog cardiac sympathetic ganglia. J Pharmacol Exp Ther. 1985 Jun;233(3):810–815. [PubMed] [Google Scholar]
  14. LARRABEE M. G., POSTERNAK J. M. Selective action of anesthetics on synapses and axons in mammalian sympathetic ganglia. J Neurophysiol. 1952 Mar;15(2):91–114. doi: 10.1152/jn.1952.15.2.91. [DOI] [PubMed] [Google Scholar]
  15. Maggi C. A., Giuliani S., Meli A. The effect of peripherally administered GABA on noradrenaline-induced reflex vagal bradycardia in urethane anaesthetized rats. Gen Pharmacol. 1985;16(6):579–584. doi: 10.1016/0306-3623(85)90146-6. [DOI] [PubMed] [Google Scholar]
  16. Maggi C. A., Manzini S., Meli A. GABA A receptor mediated neurogenic inhibition of motility in the small intestine of urethane-anaesthetized rats. Gen Pharmacol. 1986;17(2):167–171. doi: 10.1016/0306-3623(86)90134-5. [DOI] [PubMed] [Google Scholar]
  17. Maggi C. A., Meli A. Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 2: Cardiovascular system. Experientia. 1986 Mar 15;42(3):292–297. doi: 10.1007/BF01942510. [DOI] [PubMed] [Google Scholar]
  18. Maggi C. A., Santicioli P., Grimaldi G., Meli A. The effect of peripherally administered GABA on spontaneous contractions of rat urinary bladder in vivo. Gen Pharmacol. 1983;14(4):455–458. doi: 10.1016/0306-3623(83)90029-0. [DOI] [PubMed] [Google Scholar]
  19. Maggi C. A., Santicioli P., Manzini S., Meli A. Contribution of neurogenic and myogenic factors to the contractile activity of the guinea-pig distal colon in vivo and in vitro. J Auton Pharmacol. 1985 Sep;5(3):177–187. doi: 10.1111/j.1474-8673.1985.tb00118.x. [DOI] [PubMed] [Google Scholar]
  20. Maggi C. A., Santicioli P., Meli A. Dual effect of GABA on the contractile activity of the guinea-pig isolated urinary bladder. J Auton Pharmacol. 1985 Jun;5(2):131–141. doi: 10.1111/j.1474-8673.1985.tb00114.x. [DOI] [PubMed] [Google Scholar]
  21. Maggi C. A., Santicioli P., Meli A. GABAA and GABAB receptors in detrusor strips from guinea-pig bladder dome. J Auton Pharmacol. 1985 Mar;5(1):55–64. doi: 10.1111/j.1474-8673.1985.tb00565.x. [DOI] [PubMed] [Google Scholar]
  22. Manzini S., Maggi C. A., Meli A. Inhibitory effect of GABA on sympathetic neurotransmission in rabbit ear artery. Arch Int Pharmacodyn Ther. 1985 Jan;273(1):100–109. [PubMed] [Google Scholar]
  23. Mason D. T. Usefulness and limitations of the rate of rise of intraventricular pressure (dp-dt) in the evaluation of myocardial contractility in man. Am J Cardiol. 1969 Apr;23(4):516–527. doi: 10.1016/0002-9149(69)90005-8. [DOI] [PubMed] [Google Scholar]
  24. Pong S. F., Graham L. T. N-methyl bicuculline, a convulsant more potent than bicuculline. Brain Res. 1972 Jul 20;42(2):486–490. doi: 10.1016/0006-8993(72)90547-1. [DOI] [PubMed] [Google Scholar]
  25. STANTON H. C. Mode of action of gamma amino butyric acid on the cardiovascular system. Arch Int Pharmacodyn Ther. 1963 May 1;143:195–204. [PubMed] [Google Scholar]
  26. STANTON H. C., WOODHOUSE F. H. The effect of gamma-amino-n-butyric acid and some related compounds on the cardiovascular system of anesthetized dogs. J Pharmacol Exp Ther. 1960 Mar;128:233–242. [PubMed] [Google Scholar]
  27. Sangiah S., Borowitz J. L., Yim G. K. Actions of GABA, picrotoxin and bicuculline on adrenal medulla. Eur J Pharmacol. 1974 Jun;27(1):130–135. doi: 10.1016/0014-2999(74)90209-x. [DOI] [PubMed] [Google Scholar]
  28. Starke K., Weitzell R. gamma-Aminobutyric acid and postganglionic sympathetic transmission in the pulmonary artery of the rabbit. J Auton Pharmacol. 1980 Nov;1(1):45–51. doi: 10.1111/j.1474-8673.1980.tb00440.x. [DOI] [PubMed] [Google Scholar]
  29. TAKAHASHI H., TIBA M., IINO M., TAKAYASU T. The effect of gamma-aminobutyric acid on blood pressure. Jpn J Physiol. 1955 Dec 15;5(4):334–341. doi: 10.2170/jjphysiol.5.334. [DOI] [PubMed] [Google Scholar]
  30. TAKAHASHI H., TIBA M., YAMAZAKI T., NOGUCHI F. On the site of action of gamma-aminobutyric acid on blood pressure. Jpn J Physiol. 1958 Dec 20;8(4):378–390. doi: 10.2170/jjphysiol.8.378. [DOI] [PubMed] [Google Scholar]
  31. Vemulapalli S., Barletta M. The role of the sympathetic nervous system in the cardiovascular effects of systemically administered gamma-aminobutyric acid. Arch Int Pharmacodyn Ther. 1984 Jan;267(1):46–58. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES