Exposure to nitrous oxide (N₂O) increases levels of nitric oxide (NO) metabolites and β‐endorphin (β‐EP) in ventricular cisternally (VC)‐perfused rats

Abstract

Exposure to N2O has been shown to cause neuronal release of β‐EP from rat hypothalamic cells (Zuniga et al., Brain Res. 420:66, 1987). The antinociceptive of N2O in rodents is antagonized by inhibition of NO production (McDonald et al., JPET 269: 601, 1994). The present study was carried out to determine whether NO activity was increased concomitantly with the release of β‐EP in VC‐perfused rats. Male Sprague Dawley rats, 200‐250 g body weight, were anesthetized with urethane and mounted in a stereotaxic headholder. An inflow cannula was inserted into the lateral cerebral ventricle and an outflow cannula was inserted into the cisternum magnum. Artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle; perfusate fractions were collected from the cisternum and analyzed for NO metabolites and β‐EP content. Exposure to 70% N2O increased perfusate levels of nitrite and nitrate, compared to fractions collected from rats under room air. Exposure to 70% N2O also increased the concentration of β‐EP, compared to levels in fractions collected under room air. These findings indicate a functional link between increased NO activity and neuronal release of β‐EP in response to N2O and support our hypothesis that N2O may stimulate an NO‐dependent neuronal release of β‐EP. (Supported in part by State of Washington Initiative Measure No. 171 and the SURF Program in Pharmacology and Toxicology.)