Antagonism of the baroreceptor reflex by glutamate diethyl ester, an antagonist to L-glutamate.

Recent reports have suggested that the excitatory amino acid L-glutamate is a neurotransmitter released by baroreceptor afferent nerves at their termination in the nucleus tractus solitarii (NTS). In this study we have examined the effect on arterial pressure, heart rate and baroreflex activity of the glutamate antagonist glutamate diethyl ester (GDEE) microinjected into the NTS of 50 rats anesthetized with Chloralose. Bilateral injections of GDEE produced dose dependent transient hypertension. The threshold dose was 2.5 micrograms/NTS and at a dose of 15 micrograms/NTS a maximal rise in arterial pressure and heart rate (from 95 +/- 8.7 mm Hg to 153 +/- 6.4 mm Hg and from 322 +/- 14.7 beats/min to 364 +/- 16.2 beats/min respectively, P less than 0.001, n = 6) occurred. A dose of 15 micrograms/NTS also completely blocked the baroreflex when injections were made bilaterally and it totally antagonized the cardiovascular effects of L-glutamate when injected immediately prior to L-glutamate. The hypertension, the antagonism of L-glutamate, and the blockade of the baroreflex persisted for 20-30 min. In that L-glutamate mediates a baroreflex-like response upon injection into NTS and in that GDEE blocks that response while at the same time blocking the naturally occurring baroreflex, the data are consistent with L-glutamate being a neurotransmitter of baroreflex afferents.