Enhanced sensitivity of medullary depressor neurons to N-methyl-D-aspartate-glycine site antagonists in the spontaneously hypertensive rat.

1. The effects of the specific N-methyl-D-aspartate (NMDA)-glycine site antagonist 5-fluoro indole-2-carboxylic acid (FICA) and NMDA, microinjected into the vasodepressor caudal ventrolateral medulla, were compared in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto (WKY) rats. 2. 5-Fluoro indole-2-carboxylic acid elicited a significant pressor response (+20.0 +/- 4.9 mmHg) in SHR, but no change was found in the basal blood pressure of WKY rats. 3. The depressor response due to NMDA microinjection was significantly larger in SHR (-48.0 +/- 4 mmHg) than in WKY rats (-23.0 +/- 1.9 mmHg). 4. Pre-injection of FICA attenuated the depressor effects of NMDA significantly, this blockade being significantly more pronounced in SHR (37.0 +/- 2.7 mmHg) than in WKY rats (12.0 +/- 1.2 mmHg). 5. The enhanced responses to FICA may reflect the lower levels of the endogenous NMDA-glycine antagonist kynurenic acid in SHR compared with WKY rats.