Blockade of l-glutamate receptors in the rostral ventrolateral medulla contributes to ethanol-evoked impairment of baroreflexes in conscious rats

Abstract

This study investigated the effect of ethanol microinjected into the rostral ventrolateral medulla on the cardiovascular responses to in6arostral ventroleteal 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) microlrjected into the rostral ventrolateral medulla elicited pressor and bradycardic responses. The cardiovascular responses elicited by both l-glutamate and NMDA were significantly ( p < 0.05) attenuated by intrarostrel ventrolateral medulla ethanol (10 μg) or 2-amino-5 acid (2 nmoq, a selective NMDA receptor antagonist, but not by ACSF. Enhancement of the cardiovascular responses to l-glutamate by intrarostra 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 micoinjection reversed this enhancement (−290 ± 0.21 vs. −1.86 ± 0.24). Equal volume of ACSF had no effect on baroreftex 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 baroreftex sensitivity. The similarities between the inhibitory actions of ethanol and the selective NMDA receptor Mocker 2-amino-5-phosphonopentanoic acid on the cardiovascular responses to NMDA and on baroreflex sensitivity suggest that ethanol attenuates baroreflex sensitivity, at least in part, by blocking the NMDA receptors in the rostral ventrolateral medulla. This evidence is presented, for the first time, in the absence of the confounding effects of anesthetics.