NMDA receptor antagonists block cardiovascular responses to intrathecal administration of D-baclofen in the rat.
In previous studies we found that D and L-baclofen have different effects on sympathetic output when administered intrathecally, yet the actions of both enantiomers are blocked by intrathecal administration of phaclofen. The present experiments were done to determine the mechanism by which D-baclofen expresses its effects. In urethane-anaesthetized Sprague-Dawley rats, when D-baclofen was given intrathecally at the T9 spinal level following pretreatment with 2 nmol of the NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV), it increased systolic and diastolic arterial pressures (n = 7), as in the previous studies. However, after intrathecal administration of 10 nmol of APV, administration of D-baclofen had no effect on these parameters (n = 7). Intravenous administration of ketamine (7.5 mg/kg), another NMDA receptor antagonist, also blocked the effect of D-baclofen (n = 6) but it had no effect on the pressor responses produced by intrathecal administration of carbachol (27.4 nmol; n = 6). In additional experiments, L-baclofen (70 nmol) had no effect on the increases in heart rate and arterial pressure produced by N-methyl-D-aspartic acid (NMDA) (2 nmol; n = 8). These results indicate that D-baclofen increases arterial pressure via an NMDA receptor-mediated mechanism, perhaps by provoking the release of an endogenous ligand which activates these receptors.
Department of Physiology, McGill University, Montreal, Canada.
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Hong
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Henry
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D007275:Injections, Intravenous; D007278:Injections, Spinal / Q000379:methods; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013904:Thoracic Vertebrae
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007649:Ketamine; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen