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(Circulation Research. 1996;78:274-282.)
© 1996 American Heart Association, Inc.

Articles

Angiotensin II Decreases a Resting K⁺ Conductance in Rat Bulbospinal Neurons of the C1 Area

Yu-Wen Li, Patrice G. Guyenet

From the University of Virginia, Department of Pharmacology, Charlottesville, Va.

Correspondence to P.G. Guyenet, PhD, University of Virginia, Department of Pharmacology, Box 448, Health Sciences Center, Charlottesville, VA 22908. E-mail pgg@virginia.edu.

Abstract In the rostral ventrolateral medulla (RVLM), angiotensin II (Ang II) receptors are concentrated in the region that contains neurons innervating sympathetic preganglionic neurons. We sought to determine whether these bulbospinal cells are sensitive to Ang II. Retrogradely labeled bulbospinal RVLM neurons (N=125) were recorded in thin slices from neonatal rats. Most (33 of 46) histologically recovered bulbospinal neurons were C1 cells (immunoreactive for tyrosine hydroxylase [TH-ir] or phenylethanolamine N-methyltransferase [PNMT-ir]). Bulbospinal RVLM neurons were spontaneously active (2.7±0.2 spikes per second, n=69) with `resting' potential of -54±0.4 mV (n=77) and input resistance of 879±53 M (n=47). Ang II (0.3 to 1 µmol/L) increased the spontaneous firing rate of most bulbospinal neurons (+250%, 28 of 39). In current-clamp mode, Ang II (1 µmol/L) produced depolarization (+6.8±0.6 mV, n=59 neurons) and increased input resistance (+21±2%, n=36 neurons). In voltage-clamp mode, Ang II elicited an inward current (9.7±0.9 pA; holding potential, -40 to -55 mV; n=25 neurons) that reversed polarity at the K⁺ equilibrium potential (n=8 neurons) and was barium sensitive (n=4 neurons). Ang II–evoked conductance change was voltage independent (-40 to -140 mV, n=8 neurons). The effects of Ang II were blocked by losartan (9 of 9 neurons) but persisted in low Ca²⁺/high Mg²⁺ (7 of 7 neurons). Ang II–sensitive cells were inhibited by ₂-adrenergic receptor agonists (12 of 15 neurons). Ang II excited 91% (30 of 33) of TH-ir or PNMT-ir cells but 23% (3 of 13) of non–TH-ir neurons. In conclusion, RVLM bulbospinal cells express Ang II type-1 receptors whose activation leads to a reduction in resting K⁺ conductance.

Key Words: rostral ventrolateral medulla • C1 neurons • sympathetic vasomotor tone • angiotensin II • resting K⁺ conductance

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