British Journal of Anaesthesia, Vol 84, Issue 2 190-196, Copyright © 2000 by Oxford University Press
L Teppema, E Sarton, A Dahan and CN Olievier
Inhibitors of nitric oxide synthase (NOS) have analgesic properties and
reduce opioid tolerance and dependency. To investigate a possible
interaction of NOS inhibitors with the respiratory depressant action of
morphine, we determined the effects of the neuronal NOS inhibitor 7-
nitroindazole (7-NI) on the ventilatory carbon dioxide response curve;
subsequently, we studied the effects of additional morphine application.
Finally, using naloxone, we investigated a possible interaction (at the
opioid receptor) between the effects 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 dynamic end-tidal carbon dioxide forcing in eight
cats under alpha-choralose-urethane anaesthesia. Data analysis was
performed using a two-compartment model 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 from 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 apnoeic threshold by 0.5 kPa and
reduced carbon dioxide sensitivity by a further 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 morphine are mediated
independently and that the effects of 7-NI do not result from interaction
with opioid receptors.
ARTICLES
The neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) and morphine act independently on the control of breathing
Department of Physiology, Leiden University Medical Centre, The Netherlands.
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