Effects of ketamine on cardiovascular responses mediated by N-methyl-D- aspartate receptor in the rat nucleus tractus solitarius

Abstract

Background: Ketamine is often administered to patients in whom hemodynamic instability is suspected. This study was designed to investigate the effect and possible site of action of ketamine on baroreflex response in rats. The site focused upon was the N-methyl-D-aspartate (NMDA) receptor of the nucleus tractus solitarius (NTS). Methods: The effect of ketamine upon the baroreflex response was examined in urethan-anesthetized rats. The baroreflex was elicited by traction of the left carotid artery. Additional studies tested the acute hypotension and effect of ketamine on the hemodynamic response elicited by microinjection of NMDA into the NTS. Results: Upon traction, the mean arterial pressure (MAP) decreased by 28.0 ± 1.0 (mean ± SE) mmHg and the heart rate (HR) decreased by 7.5 ± 0.8 beats/min. Ketamine (9 mg/kg iv) attenuated these responses with a resultant decrease in MAP and HR of 3.6 ± 1.3 mmHg and 1.6 ± 0.2 beats/min, respectively (P < .01). It also suppressed the NMDA-induced decrease in MAP from 47 ± 5 to 6 ± 0.7 mmHg and delayed the decrease in HR. D-2-amino-5-phosphonovalerate, a competitive NMDA antagonist, blocked the NMDA-induced decrease in MAP from 47 ± 5 to 18 ± 6 mmHg and delayed the decrease in HR. Conclusions: These findings support the view that ketamine might attenuate cardiovascular responses such as baroreflex by interacting, at least in part, with the NMDA receptor in the NTS.