NMDA receptors in the nucleus of the solitary tract contribute to the splanchnic sympathoinhibitory effects of cholecystokinin

Abstract

Cholecystokinin (CCK) elicits a sympathetic vasomotor reflex that may play an important role in regulating gastrointestinal blood flow. The aim of this study was to identify the significance of excitatory amino acid (EAA) receptors in the nucleus of the solitary tract (NTS) in this reflex. We recorded arterial blood pressure, heart rate and splanchnic sympathetic nerve discharge (SSND) in halothane anesthetised, paralysed, male Sprague-Dawley rats. In separate groups of rats, the sympathoinhibitory effects of baroreflex activation (phenylephrine, PE; 10 μg/kg i.v.), von Bezold-Jarisch reflex activation (phenylbiguanide, PBG; 10 μg/kg i.v.) and CCK (4 μg/kg, i.v.) were tested before and after bilateral microinjection into the NTS of (i) the GABAA agonist muscimol (1.75mM), (ii) the EAA receptor antagonist kynurenate (55mM) and (iii) the competitive NMDA receptor antagonist AP-5 (40mM). All treatments attenuated or completely abolished the sympathoinhibitory responses to PE, PBG and CCK. Bilateral microinjection of artificial cerebrospinal fluid into the NTS was ineffective. These results indicate (i) that the NTS neurons that mediate baroreflex- and von Bezold-Jarisch reflex-sympathoinhibition overlap with those responsible for CCK-induced sympathoinhibition and (ii) both NMDA and non-NMDA receptors in the NTS are important for all three reflexes.