© 1996 American Heart Association, Inc.
Articles |
Angiotensin II Decreases a Resting K+ Conductance in Rat Bulbospinal Neurons of the C1 Area
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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