Nitric oxide synthase inhibition modulates the ventilatory depressant and antinociceptive actions of fourth ventricular infusions of morphine in the awake dog
Abstract
The role of nitric oxide (NO) production, at the brain-stem level, in ventilatory control and pain perception is poorly understood. Furthermore, it is not clear whether NO synthase (NOS) inhibition can affect morphine-induced ventilatory depression or analgesia. The central hypothesis of this investigation was that NO, at supraspinal sites, can influence ventilation and nociception and can modulate the ventilatory depressant and antinociceptive actions of morphine. Using drug delivery via the fourth cerebral ventricle, the authors examined the ventilatory and nociceptive effects of an NOS inhibitor and an NO donor in the presence or absence of morphine sulfate (MS). The studies were performed in awake dogs that were restrained in a stanchion using a fourth ventricle to cisterna magna perfusion system. The dogs were chronically prepared with fourth ventricle and cisterna magna guide cannulae, femoral arterial/venous catheters, and a tracheostomy. Agents were prepared in a temperature- and pH-controlled artificial cerebrospinal fluid, perfused at 1 ml/min through the fourth ventricle cannula, and permitted to flow out through the cisterna magna cannula. The authors measured PaCO2, ventilatory drive (inspiratory occlusion pressure...Continue Reading
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