Ketamine attenuates sympathetic activity through mechanisms not mediated by N-methyl-D-aspartate receptors in the isolated spinal cord of neonatal rats.
Ketamine is believed to have sympathomimetic effects, although the central mechanism remains unclear. Using an in vitro splanchnic nerve-spinal cord preparation from neonatal rats, our previous investigations have demonstrated that tonic sympathetic activity is spontaneously generated from the thoracic spinal cord. We designed this study to investigate whether applications of ketamine to the cord would augment sympathetic activity and whether this action was dependent on N-methyl-d-aspartate receptors. Bath application of ketamine significantly reduced sympathetic activity in a concentration-dependent manner. Ketamine in 10, 20, 40, 80, and 120 microM reduced the sympathetic activity to 82.6% +/- 4.4% (P < 0.05), 61.7% +/- 5.1%, 42.8% +/- 4.2%, 24.9% +/- 4.4%, and 9.2% +/- 2.7% of the control value, respectively (P < 0.01, n = 8 for each test). The 50% inhibitory concentration of ketamine on sympathetic activity was 32 muM. Pretreatment with DL-2-amino-5-phosphonovaleric acid, a selective competitive N-methyl-d-aspartate receptor antagonist, did not alter ketamine-induced depression of sympathetic activity. These results suggest that ketamine reduces sympathetic activity by mechanisms that are independent of N-methyl-d-aspartate receptor activity.
Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. cmho@vghtpe.gov.tw
Chiu-Ming
CM
Ho
Chun-Kuei
CK
Su
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine