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Angiotensin II stimulates spinally projecting paraventricular neurons through presynaptic disinhibition.
J Neurosci. 2003 Jun 15; 23(12):5041-9.JN

Abstract

Paraventricular nucleus (PVN) neurons that project to the spinal cord are important in the control of sympathetic outflow. Angiotensin II (Ang II) can stimulate PVN neurons, but its cellular mechanisms are not clear. In this study, we determined the effect of Ang II on the excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Whole-cell patch-clamp recordings were performed on PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Immunocytochemistry labeling revealed that the immunoreactivity of angiotensin type 1 (AT1) receptors was colocalized with a presynaptic marker, synaptophysin, in the PVN. Application of 0.1-5 microm Ang II significantly decreased the amplitude of evoked GABAergic IPSCs in a concentration-dependent manner. Also, Ang II decreased the frequency of miniature IPSCs from 2.56 +/- 0.45 to 1.05 +/- 0.20 Hz (p < 0.05; n = 12), without affecting the amplitude and the decay time constant. The effect of Ang II on miniature IPSCs was blocked by losartan but not PD123319. However, Ang II had no effect on the evoked glutamatergic EPSCs and did not alter the frequency and amplitude of miniature EPSCs at concentrations that attenuated IPSCs. Furthermore, Ang II increased the firing rate of PVN neurons from 3.75 +/- 0.36 to 7.89 +/- 0.85 Hz (p < 0.05; n = 9), and such an effect was abolished by losartan. In addition, Ang II failed to excite PVN neurons in the presence of bicuculline. Thus, this study provides substantial new evidence that Ang II excites spinally projecting PVN neurons by attenuation of GABAergic synaptic inputs through activation of presynaptic AT1 receptors.

Authors+Show Affiliations

Department of Anesthesiology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12832527

Citation

Li, De-Pei, et al. "Angiotensin II Stimulates Spinally Projecting Paraventricular Neurons Through Presynaptic Disinhibition." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 23, no. 12, 2003, pp. 5041-9.
Li DP, Chen SR, Pan HL. Angiotensin II stimulates spinally projecting paraventricular neurons through presynaptic disinhibition. J Neurosci. 2003;23(12):5041-9.
Li, D. P., Chen, S. R., & Pan, H. L. (2003). Angiotensin II stimulates spinally projecting paraventricular neurons through presynaptic disinhibition. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 23(12), 5041-9.
Li DP, Chen SR, Pan HL. Angiotensin II Stimulates Spinally Projecting Paraventricular Neurons Through Presynaptic Disinhibition. J Neurosci. 2003 Jun 15;23(12):5041-9. PubMed PMID: 12832527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II stimulates spinally projecting paraventricular neurons through presynaptic disinhibition. AU - Li,De-Pei, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, PY - 2003/7/2/pubmed PY - 2003/8/6/medline PY - 2003/7/2/entrez SP - 5041 EP - 9 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 23 IS - 12 N2 - Paraventricular nucleus (PVN) neurons that project to the spinal cord are important in the control of sympathetic outflow. Angiotensin II (Ang II) can stimulate PVN neurons, but its cellular mechanisms are not clear. In this study, we determined the effect of Ang II on the excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Whole-cell patch-clamp recordings were performed on PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Immunocytochemistry labeling revealed that the immunoreactivity of angiotensin type 1 (AT1) receptors was colocalized with a presynaptic marker, synaptophysin, in the PVN. Application of 0.1-5 microm Ang II significantly decreased the amplitude of evoked GABAergic IPSCs in a concentration-dependent manner. Also, Ang II decreased the frequency of miniature IPSCs from 2.56 +/- 0.45 to 1.05 +/- 0.20 Hz (p < 0.05; n = 12), without affecting the amplitude and the decay time constant. The effect of Ang II on miniature IPSCs was blocked by losartan but not PD123319. However, Ang II had no effect on the evoked glutamatergic EPSCs and did not alter the frequency and amplitude of miniature EPSCs at concentrations that attenuated IPSCs. Furthermore, Ang II increased the firing rate of PVN neurons from 3.75 +/- 0.36 to 7.89 +/- 0.85 Hz (p < 0.05; n = 9), and such an effect was abolished by losartan. In addition, Ang II failed to excite PVN neurons in the presence of bicuculline. Thus, this study provides substantial new evidence that Ang II excites spinally projecting PVN neurons by attenuation of GABAergic synaptic inputs through activation of presynaptic AT1 receptors. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/12832527/Angiotensin_II_stimulates_spinally_projecting_paraventricular_neurons_through_presynaptic_disinhibition_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&amp;pmid=12832527 DB - PRIME DP - Unbound Medicine ER -