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Features of GABAergic Cardiovascular Control Provided by Medullary Neurons in Rats

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Neurophysiology Aims and scope

In acute experiments on rats anesthetized with urethane, features of the involvement of GABA in medullary cardiovascular control were studied. It was found that microinjections of GABA (10–8 or 10–10 M) into the medullary nuclei (paramedian reticular nucleus, PMn, lateral reticular nucleus, LRN, and nucl. ambiguous, AMB) were accompanied by the development of either hypo- or hypertensive responses in a dose-dependent manner. There were some differences in the structure of GABA-induced hemodynamic responses. In particular, the cardiac and vascular components contributed about equally to the development of the hypotensive responses caused by GABA injections into the PMn (with significant inhibition of the heart’s chronotropic function). However, GABA-induced hypotensive responses evoked from the LRN were mainly based on the vascular component, with the a less pronounced cardiac component. GABA injections into the AMB resulted in significant decreases in the diastolic blood pressure and the heart rate. As for GABA-induced hypertensive responses originated from PMn and LRN neurons, the vascular component was predominant in their development, and chronotropic effects on the cardiac function were less pronounced. Injections of bicuculline (10–7 M), a competitive antagonist of GABAA receptors, into the medullary nuclei under investigation were accompanied by increases in both the systolic and diastolic blood pressure and heart rate. Therefore, bicuculline-sensitive GABAA receptors are involved in GABA-induced hypotensive effects. After inhibition of neuronal NO synthase, injections of GABA into the medullary nuclei did not cause the development of hypotensive responses, and GABA-induced hypertensive responses were weakened, indicating the possibility for GABA interaction with nitric oxide in nervous control of the cardiovascular system. It was also found that the effects of GABA injected into the medullary nuclei depended on the activity of Na+,K+-ATPase, the enzyme of the plasma membrane of cardiovascular neurons.

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References

  1. I A. Sytinskiy, Gamma-Aminobutyric Acid in the Nervous System Activity, Nauka, Leningrad, (1977)

  2. G. E. Fagg and A. C. Foster, “Amino acid neurotransmitters and their pathways in the mammalian central nervous system,” Neuroscience, 9, No. 4, 701–719 (1983).

    Article  CAS  PubMed  Google Scholar 

  3. L.N. Shapoval and L.S. Pobegailo, “Changes in efferent activity in the renal nerve and vegetative reactions on administration of GABA in the structures of the ventrolateral medulla in cats,” Neirofiziologya/Neurophysiology, 19, No. 3, 327–334 (1987)

    CAS  Google Scholar 

  4. W. W. Blessing, “Depressor neurons in rabbit caudal medulla act via GABA receptors in rostral medulla,” Am. J. Physiol., 23, H786–H792 (1988).

    Google Scholar 

  5. R. N. Willette, A. J. Krieger, P. P. Barcas, and H. P. Sapru, “Medullary γ-aminobutyric acid (GABA) receptors and the regulation of blood pressure in the rat,” J. Pharmacol. Exp. Ther., 226, 893–899 (1983).

    CAS  PubMed  Google Scholar 

  6. M. P. Meeley, D. A. Ruggiero, T. Ishitsuka, and D. J. Reis, “Intrinsic γ-aminobutyric acid neurons in the nucleus of the solitary tract and rostral ventrolateral medulla of the rat: immunocytochemical and biochemical study,” Neurosci. Lett., 58, 83–89 (1985).

    Article  CAS  PubMed  Google Scholar 

  7. M. Amano and T. Kubo, “Involvement of both GABAa and GABAb receptors in tonic inhibitory control of blood pressure at rostral ventrolateral medulla of the rat,” Naunyn-Schmiedeberg’s Arch. Pharmacol., 348, 146–153 (1993).

    Article  CAS  Google Scholar 

  8. A. Milner, V. M. Pickel, J. Chan, et al., “Phenylethanolamine N-ethyl-transferase-containing neurons in the rostral ventrolateral medulla. II. Synaptic relationships with GABA-ergic terminals,” Brain Res., 411, 46–57 (1987).

    Article  CAS  PubMed  Google Scholar 

  9. L. N. Shapoval, V. F. Sagach, and L. S. Pobegailo, “Chemosensitive ventrolateral medulla in the cat: the fine structure and GABA-induced cardiovascular effects,” J. Auton. Nerv. Syst., 36, 159–172 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. L. N. Shapoval, L.S. Pobeigailo, “Effect of GABA administrated in the medullary structures on the sympathetic activity and systemic arterial pressure level,” Fiziol. Zh. SSSR im. Sechenova, 68, No. 11, 1500–1505 (1982).

    CAS  Google Scholar 

  11. L. N. Shapoval, V. F. Sagach and L. S. Pobegailo, “Nitric oxide influences ventrolateral medullary mechanisms of vasomotor control in the cat,” Neurosci. Lett., 132, 47–50 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. T. I. Krukoff, “Central actions of nitric oxide in 52–65 (1999).

  13. S. Chowdhary and N. Townend, “Role of nitric oxide in the regulation of cardiovascular autonomic control,” Clin. Sci., 97, 5–17 (1999).

    Article  CAS  PubMed  Google Scholar 

  14. J. Zanzinger, “Role of nitric oxide in the neural control of cardiovascular functions,” Cardiovascul. Res., 43, 839–649 (1999).

    Google Scholar 

  15. L. N. Shapoval, V. F. Sagach, L. S. Pobegailo et al., “Involvement of nitric oxide in the medullary control of circulation in normotensive rats,” Neurophysiology, 34, No. 4, 294–302 (2002).

    Article  Google Scholar 

  16. L. N. Shapoval, “Nitric oxide and nervous control of cardiovascular function,” in: Receptors, Channels and Messengers, P. G. Kostyuk and E. A. Lukyanetz, (eds.), DUS, Kiev (2005), pp. 318–337.

    Google Scholar 

  17. L. N. Shapoval, О. V. Dmytrenko, L. S. Pobegailo et al., “Hemodynamic responses induced by modulated nitric oxide system and mitochondrial permeability transition in the medullary cardiovascular neurons in rats,” Neurophysiology, 39, № 3, 232–244 (2007).

    Article  Google Scholar 

  18. T. Kishi, Y. Hirooka, K. Sakai, et al., “Overexpression of eNOS in the RVLM causes hypertension and bradycardia via GABA release,” Hypertension, 38, No. 4, 896–904 (2001).

    CAS  PubMed  Google Scholar 

  19. K. S. Rayevsky and V.P. Georgiev, Mediator Amino Acids: Neuropharmacological and Neurochemical Aspects, Meditsina, Moscow, Sofia (1986).

  20. M. Chebib and G. A. R. Johnston, “GABA-activated ligand-gated ion channels: medical chemistry and molecular biology,” J. Med. Chem., 43, No. 8, 1427–1447 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. A.A. Boldyrev, “The role of Na/K- pump in excitable tissues (review),” J. Sib. Fed. Univ. Biol., 3, 208–225 (2008).

    Google Scholar 

  22. J. B. Lingrel and T. Kuntzweiler, “Na/K-АТPase,” J. Biol. Chem., 269, 19659–19662 (1994).

    CAS  PubMed  Google Scholar 

  23. K. Ikeda, H. Onimaru, J. Jamada, et al., “Malfunction of respiratory-related neuronal activity in Na+-K+-АТPase α2 subunit-deficient mice is attributable to abnormal Clhomeostasis in brainstem neurons,” J. Neurosci., 24, No. 47, 10693–10701 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. G. Paxinos and C. Walson, The Rat Brain in Stereotaxic Coordinates, Academic Press, New York (1982).

    Google Scholar 

  25. D. R. Curtis, A. W. Duggan, D. Felix, and G. A. R. Johnston, “Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat,” Brain Res., 32, 69–96 (1971)

    Article  CAS  PubMed  Google Scholar 

  26. A. S. Padilha, M. Salaices, S. D. V. Vassallo, et al., “Hypertensive effects of the i.v. administration of picomoles of ouabain,” Brazil. J. Med. Biol. Res., 44, 933–938 (2011).

    Article  CAS  Google Scholar 

  27. M. Ferrandi, P. Barassi, I. Molinari, et al., “Ouabain antagonists as antihypertensive agents,” Curr. Pharm. Res., 11, No 25, 3301–3305 (2005).

    Article  CAS  Google Scholar 

  28. X. Hou, S. T. Theriault, I. Dostanic-Larson, et al., “Enhanced pressor response to increased CSF sodium concentration and to central ANG 1 in heteroxygous α2 Na+-K+-АТPase knockout mice,” Am. J. Physiol. Regulat. Integr. Comp. Physiol., 296, R1427–R1438 (2009).

    Article  CAS  Google Scholar 

  29. H. Takahashi, M. Yoshika, Yu. Komiyama, and M. Nishimura, “The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain,” Hypertens. Res., 34, 1147–1160 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. J. C. Wang, J. A. Staessen, E. Messaggio, et al., “Salt, endogenous ouabain and blood pressure interactions in the general population,” J. Hypertens., 21, No. 8, 1475–1481 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. J. Zhang, M. Y. Lee, M. Cavalli, et al., “Sodium pump alpha 2 subunits control myogenic tone and blood pressure in mice,” J. Physiol., 569, Part 1, 243–256 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. B. S. Huang and F. H. Leenen, “Blockade of brain ‘ouabain’ prevents sympathoexcitatory and pressor responses to high sodium in SHR,” Am. J. Physiol., 271, Y103–H108 (1996).

    Google Scholar 

  33. A. Aydemir-Koksoy, J. Abramovitz, and J. C. Allen, “Ouabain-induced signaling and vascular smooth muscle cell proliferation,” J. Biol. Chem., 276, 46605–46611 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. L. N. Shapoval, O.V. Dmytrenko, G.L. Vavilova et al. “Effect of modulation of Na+,K+-ATPase in the medullary cardiovascular neurons on hemodynamic effects in spontaneously hypertensive rats,” Fіzіol. Zh., 58, No 5, 3–13 (2012).

    CAS  Google Scholar 

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Radchenko, N.V., Shapoval, L.N., Davydovskaya, T.L. et al. Features of GABAergic Cardiovascular Control Provided by Medullary Neurons in Rats. Neurophysiology 45, 407–416 (2013). https://doi.org/10.1007/s11062-013-9386-1

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