Bilateral blockade of angiotensin (Ang) receptors in the rostral ventrolateral medulla (RVLM) causes a profound fall in arterial pressure. In this study, we tested whether this effect is due to an interaction between Ang receptors and either glutamatergic or γ-aminobutyric acidergic (GABAergic) synaptic inputs to RVLM sympathoexcitatory neurons. In urethane-anaesthetised rats, bilateral microinjections of the Ang receptor antagonists [Sar1,Thr8]Ang II or [Sar1,Ile8]Ang II into the RVLM pressor region caused large decreases in arterial pressure, heart rate and renal sympathetic nerve activity (RSNA). These responses were not significantly altered following bilateral microinjections into the RVLM of the glutamate receptor antagonist kynurenic acid (4.5 nmol). Furthermore, bilateral injections of kynurenic 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 microinjections of [Sar1,Ile8]Ang II. However, the level of arterial pressure and RSNA following bilateral injections of kynurenic acid, bicuculline and [Sar1,Ile8]Ang II were similar to the levels before injection of any of these compounds. The effectiveness of the microinjections of kynurenic acid and bicuculline into the RVLM was demonstrated by the observation that they virtually abolished the somato-sympathoexcitatory and baroreceptor-sympathoinhibitory reflexes, which are mediated by glutamatergic and GABAergic synapses, respectively, in the RVLM. These results indicate that (1) blockade of Ang receptors greatly reduces the firing rate of RVLM sympathoexcitatory neurons via a mechanism that is independent of glutamatergic or GABAergic neurotransmission, and (2) in the absence of inputs mediated by ionotropic glutamate, GABA(A) and Ang receptors, there are other mechanisms which generate a level of tonic activity in RVLM sympathoexcitatory neurons sufficient to maintain a normal level of sympathetic vasomotor activity. Copyright (C) 1999 Elsevier Science B.V.
- Angiotensin antagonist
- Arterial pressure
- Renal sympathetic nerve activity
- Rostral ventrolateral medulla