Sympathoinhibition after angiotensin receptor blockade in the rostral ventrolateral medulla is independent of glutamate and gamma-aminobutyric acid receptors

Bilateral blockade of angiotensin (Ang) receptors in the rostral ventrolate ral medulla (RVLM) causes a profound fall in arterial pressure, In this stu dy, we tested whether this effect is due to an interaction between Ang rece ptors and either glutamatergic or gamma-aminobutyric acidergic (GABAergic) synaptic inputs to RVLM sympathoexcitatory neurons. In urethane-anaesthetis ed rats, bilateral microinjections of the Ang receptor antagonists [Sar(1), Thr(8)]Ang II or [Sar(1),Ile(8)]Ang II into the RVLM pressor region caused large decreases in arterial pressure, heart rate and renal sympathetic nerv e activity (RSNA). These responses were not significantly altered following bilateral microinjections into the RVLM of the glutamate receptor antagoni st kynurenic acid (4.5 nmol). Furthermore, bilateral injections of kynureni c acid plus the GABA(A) receptor antagonist bicuculline (200 pmol) into the RVLM increased the baseline arterial pressure and RSNA, but did not alter the percentage decreases in these variables evoked by bilateral microinject ions of [Sar(1),Ile(8)]Ang II. However, the level of arterial pressure and RSNA following bilateral injections of kynurenic acid, bicuculline and [Sar (1),Ile(8)]Ang II were similar to the levels before injection of any of the se compounds. The effectiveness of the microinjections of kynurenic acid an d bicuculline into the RVLM was demonstrated by the observation that they v irtually abolished the somato-sympathoexcitatory and baroreceptor-sympathoi nhibitory reflexes, which are mediated by glutamatergic and GABAergic synap ses, respectively, in the RVLM. These results indicate that (1) blockade of Ang receptors greatly reduces the firing rate of RVLM sympathoexcitatory n eurons via a mechanism that is independent of glutamatergic or GABAergic ne urotransmission, and (2) in the absence of inputs mediated by ionotropic gl utamate, GABA(A) and Ang receptors, there are other mechanisms which genera te a level of tonic activity in RVLM sympathoexcitatory neurons sufficient to maintain a normal level of sympathetic vasomotor activity. (C) 1999 Else vier Science B.V. All rights reserved.