ROLE OF BRAIN INTERSTITIAL ADENOSINE IN HYPOXIC VENTILATORY DEPRESSION

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The purpose of this study is to elucidate the time-dependent change of endogenous adenosine levels in the brain during moderate sustained hypoxia, and to examine its possible relationship with the ventilatory depression seen in the latter falf of sustained hypoxia. In 10 spontaneously breathing cats (carotid sinus and vagal nerve intact), the interstitial levels of adenosine were estimated by a microdialysis method in frontal cortex and nucleus tractus solitarius (NTS) before and during 40 min isocapnic hypoxia (mean PaO2 = 38.3 Torr). The adenosine levels reversibly increased during hypoxia both in the cortex (from 0.70 (〕SY.+-.〔) 0.10 SE to 1.09 (〕SY.+-.〔) 0.13 muM, P <0.05) and in the NTS (from 0.53 (〕SY.+-.〔) 0.08 to 0.95 (〕SY.+-.〔) 0.19 muM, P <0.05) without a significant difference between the two regions. There was a significant positive correlation between the relative rise of adenosine only in the NTS and the relative decline of ventilation after its peak during sustained hypoxia(r=0.70, P<0.05), which may support the hypothesis that the interstitial adenosine in the medulla is involved in the development of hypoxic ventilatory depression in cats.