This study investigated the effect of ethanol microinjected into the rostral ventrolateral medulla on the cardiovascular responses to intrarostral ventrolateral medulla administration of the excitatory amino acids L-glutamate and N-methyl-D-aspartate (NMDA) and on baroreflex-mediated heart rate responses (baroreflex sensitivity) in conscious freely moving Sprague-Dawley rats. L-Glutamate (5 nmol) or NMDA (25, 50, and 100 pmol) microinjected into the rostral ventrolateral medulla elicited pressor and bradycardiac responses. The cardiovascular responses elicited by both L-glutamate and NMDA were significantly (p < 0.05) attenuated by intrarostral ventrolateral medulla ethanol (10 micrograms) or 2-amino-5-phosphonopentanoic (2 nmol), a selective NMDA receptor antagonist, but not by ACSF. Enhancement of the cardiovascular responses to L-glutamate by intrarostral ventrolateral medulla p-chloromercuriphenylsulfonic acid (0.1 nmol), a glutamate uptake inhibitor, was reversed by subsequent ethanol, but not ACSF, microinjection. None of the treatments influenced baseline blood pressure or heart rate. Ethanol or 2-amino-5-phosphonopentanoic acid microinjected into the rostral ventrolateral medulla significantly (p < 0.05) attenuated baroreflex sensitivity tested by phenylephrine. In contrast, p-chloromercuriphenylsulfonic acid significantly (p < 0.05) enhanced baroreflex sensitivity (-2.14 +/- 0.09 vs. -3.08 +/- 0.18); subsequent ethanol microinjection reversed this enhancement (-2.90 +/- 0.21 vs. -1.86 +/- 0.24). Equal volume of ACSF had no effect on baroreflex sensitivity of pretreated rats (-3.22 +/- 0.31 vs. -2.98 +/- 0.34). These results suggest that ethanol exerts a marked inhibitory action on glutamatergic pathways within the rostral ventrolateral medulla that act to enhance baroreflex sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)