CIRCULATING ENDOTHELIN INFLUENCES AREA POSTREMA NEURONS

The recently described endothelium-derived constricting factor endothelin (ET) is a 21 amino acid peptide which is the most potent endogenous vasoconstrictor yet described. Binding sites for this peptide have been demonstrated within the circum-ventricular structures of the brain. One of these structures, the area postrema (AP), has been implicated in central cardiovascular control mechanisms. We have recently demonstrated that microinjection of ET into this structure results in dose-dependent changes in mean arterial blood pressure. The present studies were undertaken to test the hypothesis that ET elicits these effects as a result of influences on the activity of AP neurons. Using extracellular single unit recording techniques we have examined the effects of systemic administration of ET on the activity of AP neurons. A total of 60 AP neurons were tested for effect of ET (0.1-10.0 pmol) of which the spontaneous activity of 32 showed rapid (modified frequency of action potentials in the 60 s following ET), reversible (return to baseline activity within 10 m) responses to this peptide. The initial response of the majority (84%) of AP neurons influenced by ET was excitatory, while a small proportion of AP neurons were inhibited (16%) by systemic administration of this peptide. We have also examined whether such excitatory effects were specific to AP neurons by comparing the above response characteristics to those observed in neurons in the adjacent commissural NTS. Such recordings demonstrated predominantly inhibitory (84% of influenced cells) responses of this group of NTS neurons to ET. While these findings demonstrate specific excitatory effects of systemic ET on the activity of AP neurons they also suggest a potential role for this peptide in controlling the activity of NTS neurons. These studies provide evidence that circulating ET influences AP neuronal function, although they offer no definitive information as to the specific site of action.