Isoflurane enhances glutamatergic agonist-stimulated nitric oxide synthesis in cultured neurons

The purpose of this study was to determine how halothane, isoflurane, and enflurane, three commonly used volatile anesthetic agents, affect glutamate receptor-modulated nitric oxide signaling in cultured cortical neurons. Primary cultures of cortical neurons were prepared from fetal Sprague-Dawley rats and experiments were performed after 11-13 days in culture. Cyclic GMP was measured as an indicator of nitric oxide production. Glutamate (100 microM), N-methyl-D-aspartate (100 microM), quisqualate (300 microM), or kainate (100 microM) increased cyclic GMP production. At clinically relevant concentrations, isoflurane enhanced responses to each of these agonists, while halothane or enflurane had no effect. Thus, isoflurane, but not halothane or enflurane, enhanced nitric oxide signaling stimulated by glutamatergic agonists.