Dexamethasone attenuates the depressor response induced by neuropeptide Y microinjected into the nucleus tractus solitarius in rats

Abstract

An investigation was made of the effect of dexamethasone (Dex) injection into the nucleus tractus solitarius (NTS) on the cardiovascular response to neuropeptide Y in rats. Dex (39 pmol) injected into the NTS inhibited the hypotension and bradycardia caused by NPY (5 pmol) with a short latency (10 min) and a long duration of action (up to 4 h). The rapid inhibition by Dex (39 pmol) of the cardiovascular response to NPY was not blocked by pretreatment with the glucocorticoid receptor blocker, RU38486 (47 or 117 pmol respectively), but was reversed by bicuculline (30 pmol). Microiontophoresis of NPY (0.01 mM, pH 6.5) into the NTS increased the spontaneous firing of the majority (68.4%) of baroreflex-excited cells, but decreased the firing of most (73.7%) baroreflex-inhibited cells. In contrast, Dex (0.02 M, pH 6.5) decreased the spontaneous firing of the majority of baroreflex-excited cells (42.1% of normal response) and decreased the inhibition of baroreflex-inhibited cells (47.5% of normal response). The responses of the majority of baroreceptive cells to NPY were blocked by iontophoretic administration of Dex. Dex (200 microM) increased the delayed rectifier outward K+ current by 31.4+/-1.1% (n=5), whereas NPY alone, at a concentration of 1.5 microM, inhibited the current by 28.6+/-0.8% (n=5). In the presence of Dex (200 microM), addition of NPY (1.5 microM) had no effect on the current. In conclusion, NTS-administered-Dex attenuated the cardiovascular response to NPY injected into the same area via a rapid membrane effect, which was mediated by an action on GABA(A) receptors and on the delayed rectifier outward K(+) channel.

Figure 1

Effect of Dex on changes of blood pressure induced by microinjection of NPY into the NTS. [right to left hatched box] NPY (5 pmol) alone microinjected into the NTS; [vertical lined box] NPY (5 pmol) and Dex (20 ng) coinjected into the NTS; [horizontal lined box] NPY (5 pmol) microinjected into the NTS 10 min after pretreatment with Dex (20 ng); [open box] NPY (5 pmol) microinjected into the NTS 30 min after pretreatment with Dex (20 ng); [cross-hatched box] NPY (5 pmol) microinjected into the NTS 60 min after pretreatment with Dex (20 ng); [dotted box]NPY (5 pmol) microinjected into the NTS 120 min after pretreatment with Dex (20 ng); [left to right hatched box] NPY (5 pmol) microinjected into the NTS 180 min after pretreatment with Dex (20 ng); [filled box] NPY (5 pmol) microinjected into the NTS 240 min after pretreatment with Dex (20 ng).

Figure 2

Effect of Dex on changes of heart rate induced by microinjection of NPY into the NTS. [right to left hatched box] NPY (5 pmol) alone injected into the NTS; [vertical lined box] NPY (5 pmol) and Dex (20 ng) coinjected into the NTS; A: NPY (5 pmol) microinjected into the NTS 10 min after Dex (20 ng) administered into the same area; [horizontal lined box] NPY (5 pmol) microinjected into the NTS 30 min after Dex (20 ng) administered into the same area; B: NPY (5 pmol) microinjected into the NTS 60 min after Dex (20 ng) administered into the same area; [cross-hatched box] NPY (5 pmol) microinjected into the NTS 120 min after Dex (20 ng) administered into the same area; [left to right hatched box] NPY (5 pmol) microinjected into the NTS 180 min after Dex (20 ng) administered into the same area; [filled box] NPY (5 pmol) microinjected into the NTS 240 min after Dex (20 ng) administered into the same area.

Figure 3

Baroreceptive cells in the NTS response to arterial blood pressure elevated. (A) Arterial blood pressure changed after injection of phenylephrine; (B) Baroreflex-excited cell; (C) Baroreflex-inhibited cell.

Figure 4

Effects of NPY and Dex on the activities of baroreceptive cells in the NTS. (A) Baroreflex-inhibited cell; (B) Baroreflex-excited cell.

Figure 5

Delayed rectifier outward potassium current. (A) Current records in response to depolarization in steps from −80 to +30 mV; (B) Current records under addition of TEA (10 mM); (C) Current-voltage relation of steady state delayed rectifier outward potassium current for five cells.

Figure 6

Effects of Dex and NPY on the delayed rectifier outward potassium currents of acutely dissociated neuron in the NTS. (A) Current records in response to depolarization in steps from −80 to +30 mV under normal extracellular solution; (B) Current response to addition of Dex (200 μM) into the extracellular solution; (C) Current response to addition of NPY (1.5 μM) into the extracellular solution; (D) Current response to addition of NPY (1.5 μM) into the extracellular solution after pretreatment with Dex (200 μM).