The neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) and morphine act independently on the control of breathing

Inhibitors of nitric oxide synthase (NOS) have analgesic properties and red uce opioid tolerance and dependency. To investigate a possible interaction of NOS inhibitors with the respiratory depressant action of morphine, we de termined the effects of the neuronal NOS inhibitor 7-nitroindazole (7-NI) o n the ventilatory carbon dioxide response curve; subsequently, we studied t he effects of additional morphine application. Finally, using naloxone, we investigated a possible interaction (at the opioid receptor) between the ef fects of 7-NI and morphine. The effects of 7-NI 50 mg kg(-1) i.p., morphine 0.1 mg kg(-1) i.v. and naloxone 0.1 mg kg(-1) i.v. were studied using dyna mic end-tidal carbon dioxide forcing in eight cats under alpha-choralose-ur ethane anaesthesia. Data analysis was performed using a two-compartment mod el comprising a fast peripheral and a slow central component characterized by carbon dioxide sensitivities and a single offset B (apnoeic threshold). 7-NI decreased the mean apnoeic threshold from 4.27 (SD 0.87) to 2.59 (1.71 ) kPa. Peripheral and central carbon dioxide sensitivities were reduced fro m 0.56 (0.22) to 0.26 (0.09) litre min(-1) kPa(-1) and from 0.09 (0.05) to 0.04 (0.03) litre min(-1) kPa(-1) respectively. Morphine increased the apno eic threshold by 0.5 kPa and reduced carbon dioxide sensitivity by a furthe r 35%. Naloxone reversed the ventilatory effects of morphine but not those induced by 7-NI. We conclude that the respiratory effects of 7-NI and morph ine are mediated independently and that the effects of 7-NI do not result f rom interaction with opioid receptors.