Effect of nitric oxide in the nucleus isthmi on the hypoxic and hypercarbic drive to breathing of toads

Nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain tha t has been reported to participate in CO2 chemoreception and in the ventila tory response to hypoxia. However, no information exists about the modulato rs and/or mediators involved. In the present study, we assessed the partici pation of nitric oxide (NO) in the hypoxic and hypercarbic drive to breathi ng, specifically in the NI. We compared the ventilatory and cardiovascular responses with hypoxia and hypercarbia after microinjecting 100 nmol/0.5 mu l of N-G-nitro-L-arginine methyl ester (L-NAME; an NO synthase blocker) int o the NI of toads (Bufo paracnemis). L-NAME had no effect under resting con ditions. Hypoxia elicited an increase in ventilation in control and vehicle toads by elevating tidal volume (V-T). Hypercarbia caused hyperventilation in all groups due to an increase in both V-T and frequency. The microinjec tion of L-NAME into the NI elicited an increase in ventilatory response to hypoxia and hypercarbia due to a higher V-T. We conclude that NO in the NI has an inhibitory effect when the respiratory drive is high, acting on V-T.