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Angiotensin II attenuates synaptic GABA release and excites paraventricular-rostral ventrolateral medulla output neurons.
J Pharmacol Exp Ther. 2005 Jun; 313(3):1035-45.JP

Abstract

The hypothalamic paraventricular nucleus (PVN) neurons regulate sympathetic outflow through projections to the spinal cord and rostral ventrolateral medulla (RVLM). Although the PVN-RVLM pathway is important for the action of brain angiotensin II (Ang II) on autonomic control, the cellular mechanisms involved are not fully known. In this study, we examined the effect of Ang II on the excitability and synaptic inputs to RVLM-projecting PVN neurons. PVN neurons were retrogradely labeled by FluoSpheres injected into the RVLM of rats. Whole-cell patch-clamp recordings were performed on labeled PVN neurons in brain slices. Ang II significantly increased the firing rate of PVN neurons from 3.63 +/- 0.65 to 6.10 +/- 0.75 Hz (P < 0.05, n = 9), and such an effect was eliminated by an AT(1) receptor antagonist, losartan. Furthermore, inclusion of a G protein inhibitor, guanosine 5'-O-(2-thiodiphosphate, in the pipette internal solution did not alter the excitatory effect of Ang II on labeled PVN neurons. Application of 0.5 to 5 microM Ang II significantly decreased the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs) in a dose-dependent manner. Also, 2 microM Ang II significantly decreased the frequency of miniature IPSCs (mIPSCs) from 3.89 +/- 0.84 to 2.06 +/- 0.45 Hz (P < 0.05, n = 11), but did not change the amplitude and decay time constant of mIPSCs. By contrast, Ang II had no significant effect on glutamatergic excitatory postsynaptic currents at the concentrations that inhibited IPSCs. In addition, Ang II failed to excite PVN neurons in the presence of bicuculline. Collectively, this study provides important new information that Ang II excites RVLM-projecting PVN neurons through attenuation of GABAergic synaptic inputs.

Authors+Show Affiliations

Department of Anesthesiology, Pennsylvania State University College of Medicine, Hershey, 17033, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15681656

Citation

Li, De-Pei, and Hui-Lin Pan. "Angiotensin II Attenuates Synaptic GABA Release and Excites Paraventricular-rostral Ventrolateral Medulla Output Neurons." The Journal of Pharmacology and Experimental Therapeutics, vol. 313, no. 3, 2005, pp. 1035-45.
Li DP, Pan HL. Angiotensin II attenuates synaptic GABA release and excites paraventricular-rostral ventrolateral medulla output neurons. J Pharmacol Exp Ther. 2005;313(3):1035-45.
Li, D. P., & Pan, H. L. (2005). Angiotensin II attenuates synaptic GABA release and excites paraventricular-rostral ventrolateral medulla output neurons. The Journal of Pharmacology and Experimental Therapeutics, 313(3), 1035-45.
Li DP, Pan HL. Angiotensin II Attenuates Synaptic GABA Release and Excites Paraventricular-rostral Ventrolateral Medulla Output Neurons. J Pharmacol Exp Ther. 2005;313(3):1035-45. PubMed PMID: 15681656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II attenuates synaptic GABA release and excites paraventricular-rostral ventrolateral medulla output neurons. AU - Li,De-Pei, AU - Pan,Hui-Lin, Y1 - 2005/01/28/ PY - 2005/2/1/pubmed PY - 2005/7/15/medline PY - 2005/2/1/entrez SP - 1035 EP - 45 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 313 IS - 3 N2 - The hypothalamic paraventricular nucleus (PVN) neurons regulate sympathetic outflow through projections to the spinal cord and rostral ventrolateral medulla (RVLM). Although the PVN-RVLM pathway is important for the action of brain angiotensin II (Ang II) on autonomic control, the cellular mechanisms involved are not fully known. In this study, we examined the effect of Ang II on the excitability and synaptic inputs to RVLM-projecting PVN neurons. PVN neurons were retrogradely labeled by FluoSpheres injected into the RVLM of rats. Whole-cell patch-clamp recordings were performed on labeled PVN neurons in brain slices. Ang II significantly increased the firing rate of PVN neurons from 3.63 +/- 0.65 to 6.10 +/- 0.75 Hz (P < 0.05, n = 9), and such an effect was eliminated by an AT(1) receptor antagonist, losartan. Furthermore, inclusion of a G protein inhibitor, guanosine 5'-O-(2-thiodiphosphate, in the pipette internal solution did not alter the excitatory effect of Ang II on labeled PVN neurons. Application of 0.5 to 5 microM Ang II significantly decreased the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs) in a dose-dependent manner. Also, 2 microM Ang II significantly decreased the frequency of miniature IPSCs (mIPSCs) from 3.89 +/- 0.84 to 2.06 +/- 0.45 Hz (P < 0.05, n = 11), but did not change the amplitude and decay time constant of mIPSCs. By contrast, Ang II had no significant effect on glutamatergic excitatory postsynaptic currents at the concentrations that inhibited IPSCs. In addition, Ang II failed to excite PVN neurons in the presence of bicuculline. Collectively, this study provides important new information that Ang II excites RVLM-projecting PVN neurons through attenuation of GABAergic synaptic inputs. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15681656/Angiotensin_II_attenuates_synaptic_GABA_release_and_excites_paraventricular_rostral_ventrolateral_medulla_output_neurons_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=15681656 DB - PRIME DP - Unbound Medicine ER -