Pharmacological blockade of neuronal nitric oxide synthase (nNOS) is ineffective in altering the acute hypoxic ventilatory response in arterially‐perfused adult rat

Endogenously produced nitric oxide (NO) has been shown to alter hypoxic ventilatory responses (HVR), albeit the role of neuronal NO in this modulation appears to be varied across species, preparations, developmental ages, and the severity and duration of the hypoxic stimulus. Previous work from our laboratory has focused on the effects of blockade of nNOS on anoxic/ischemic ventilatory responses in an arterially‐perfused adult rat preparation; however, the results from this work are confounded by the effects of systemic hypoxia. To better understand the role of neuronal NO in this preparation on the acute HVR evoked by carotid chemoreceptor stimulation, we examined phrenic nerve discharge in response to sodium cyanide (NaCN) injection before and after blockade of nNOS with S‐methyl‐L‐thiocitrulline (SMTC) in 9 preparations. Under both control conditions and during perfusion with SMTC, the NaCN‐induced HVR was characterized by an increase in phrenic burst amplitude (~60%) and frequency (~90%), with the latter mediated by reductions in both T I and T E , and a shift in T peak to earlier in the burst. Perfusion with SMTC, however, was ineffective in further altering HVR parameters. These data indicate that neuronal NO does not play a significant role in the NaCN‐induced HVR in this preparation, and suggest that neuronal NO differentially affects centrally‐ and peripherally‐mediated HVR behaviors. Supported by HL63175