The effect of acute hypoxemia and hypotension on adenosine-mediated depression of evoked hippocampal synaptic transmission

Abstract

The present study was designed to investigate the relative contributions of arterial P O 2 , local cerebral blood flow, and oxygen delivery to the adenosine A 1 receptor-mediated depression of evoked synaptic transmission recorded in the rat hippocampus. Urethane-anesthetized rats were given a unilateral common carotid artery occlusion and then placed in a stereotaxic apparatus for stimulation and recording of bilateral hippocampal field excitatory postsynaptic potentials (fEPSPs). Arterial blood gases, mean arterial blood pressure (MAP), and bilateral hippocampal blood flow (HBF) were also measured. Arterial P O 2 , HBF, and oxygen delivery were manipulated using normoxic hypotension, hypoxic hypotension, and hypoxic normotension. Both hypoxic hypotension and normoxic hypotension resulted in decreased HBF, decreased oxygen delivery, and a depression of the evoked fEPSP limited to the hippocampus ipsilateral to the occlusion. The enhanced HBF and oxygen delivery associated with increased MAP resulted in a restoration and maintenance of hippocampal fEPSPs despite sustained hypoxemia. The adenosine A 1 receptor-mediated depression of the fEPSP was more strongly correlated with changes in HBF and oxygen delivery than with arterial P O 2 . We propose that adenosine plays an important role mediating the depression of neuronal activity associated with reduced oxygen delivery characteristically observed in ischemic brain tissue.