MECHANISM OF THE CARDIOVASCULAR EFFECTS OF GABA(B) RECEPTOR ACTIVATION IN THE NUCLEUS TRACTUS SOLITARII OF THE RAT

The effects of baclofen microinjected into the nucleus tractus solitarii (NTS) on blood pressure, heart rate and baroreflex bradycardia were studied in urethane-anesthetized rats. Baclofen caused dose-dependent pressor and tachycardic effects and inhibited the reflex bradycardia elicited by i.v. phenylephrine. The effects of baclofen were inhibited by similarly administered GABA(B) receptor antagonists, phaclofen and 2-OH-saclofen, or the non-NMDA glutamate receptor antagonist, DNQX, or by pretreatment of rats with intracisternally administered pertussis toxin. DNQX and pertussis toxin, but not the NMDA antagonist, MK-801, also inhibited baroreflex bradycardia. Intra-NTS injections of glutamate caused hypotension and bradycardia, which were potentiated by baclofen, and were not affected by either DNQX or MK-801, or by pretreatment with pertussis toxin. These findings indicate that the cardiovascular effects of stimulation of GABA(B) receptors in the NTS are due, at least in part, to inhibition of the depressor baroreflex response. Inhibition of the release and/or postsynaptic action of an excitatory amino acid transmitter other than glutamate is the most likely mechanism.