Nitric Oxide Synthase Inhibitors Alter Ventilation in Isoflurane Anesthetized Rats

Background: Nitric oxide (NO) is present in medullary structures and can modulate respiratory rhythm. The authors determined if spontaneous ventilation at rest and in response to increased carbon dioxide is altered by selective neuronal NO synthase (NOS; 7-nitro-indazole, 7-NI) or nonselective (neuronal plus endothelial) NOS (NG -L-arginine methyl ester [L-NAME] and NG -monomethyl L-arginine [L-NMMA]) inhibitors in rats anesthetized with isoflurane.

Methods: Fifty-four rats received either L-NAME or L-NMMA (1, 10, and 30 mg/kg) or 7-NI (20, 80, and 400 mg/kg) and were compared with time controls (isoflurane = 1.4%), with isoflurane concentrations (1.6%, 1.8%, and 2%) increased consistent with the increased anesthetic depth caused by NOS inhibitors, or with L-arginine (300 mg/kg). Tidal volume (VT), respiratory frequency (f), minute ventilation (V with dotE), and ventilatory responses to increasing carbon dioxide were determined.

Results: L-NAME and L-NMMA decreased resting VT and V with dot (E), whereas 7-NI had no effect. Increasing concentrations of isoflurane decreased resting f, VT, and V with dotE. L-NAME and L-NMMA decreased VT and V with dotE, whereas 7-NI had no effect at 8%, 9%, and 10% end-tidal carbon dioxide (ETCO2). Increasing concentrations of isoflurane decreased f, VT, and V with dotE at 8%, 9%, and 10% ETCO2. The slope of V with dotE versus ETCO2 was decreased by isoflurane but was unaffected by L-NAME, L-NMMA, or 7-NI. L-arginine alone had no effect on ventilation.