Signaling mechanisms of angiotensin II-induced attenuation of GABAergic input to hypothalamic presympathetic neuronsJournal of neurophysiology
AbstractThe hypothalamic paraventricular nucleus (PVN) is an important site for the regulation of sympathetic outflow. Angiotensin II (Ang II) can activate AT 1 receptors to stimulate PVN presympathetic neurons through inhibition of GABAergic input. However, little is known about the downstream pathway involved in this presynaptic action of Ang II in the PVN. In this study, using whole cell recording from retrogradely labeled PVN neurons in rat brain slices, we determined the signaling mechanisms responsible for the effect of Ang II on synaptic GABA release to spinally projecting PVN neurons. Bath application of Ang II reproducibly decreased the frequency of GABAergic miniature postsynaptic inhibitory currents (mIPSCs) in fluorescence-labeled PVN neurons. Ang II failed to change the frequency of mIPSCs in labeled PVN neurons treated with pertussis toxin. However, Ang II-induced inhibition of mIPSCs persisted in the presence of either CdCl2, a voltage-gated Ca 2+ channel blocker, or 4-aminopyridine, a blocker of voltage-gated K+ channels. Interestingly, inhibition of superoxide with superoxide dismutase or Mn(III) tetrakis (4-benzoic acid) prophyrin completely blocked Ang II-induced decrease in mIPSCs. By contrast, inhibition of hydroxyl radical formation with the ion chelator deferoxamine did not significantly alter the effect of Ang II. These findings suggest that the presynaptic action of Ang II on synaptic GABA release in the PVN is mediated by the pertussis toxin-sensitive Gi/o proteins but not by voltage-gated Ca2+ and K + channels. Ang II attenuates GABAergic input to PVN presympathetic neurons through reactive oxygen species, especially superoxide anions. Copyright Â© 2007 The American Physiological Society.
Citation InformationQian Chen and H. L. Pan. "Signaling mechanisms of angiotensin II-induced attenuation of GABAergic input to hypothalamic presympathetic neurons" Journal of neurophysiology Vol. 97 Iss. 5 (2007) p. 3279 - 3287
Available at: http://works.bepress.com/qian_chen/32/