ENDOTHELIN ACTS AT THE SUBFORNICAL ORGAN TO INFLUENCE THE ACTIVITY OF PUTATIVE VASOPRESSIN AND OXYTOCIN-SECRETING NEURONS

Systemic endothelin-1 (ET-1) enhances the activity of subfornical organ (SFO) neurons with identified projections to the paraventricular nucleus of the hypothalamus (PVN). The present electrophysiological experiments were undertaken to examine the mechanisms through which systemic ET influences vasopressin secretion. Systemic ET-1 (50-100 pmol) was found to influence the excitability of antidromically identified vasopressin and oxytocin-secreting neurons in the PVN or supraoptic nucleus (SON) of urethane-anaesthetized rats. Long-term stable recordings from 95 antidromically identified neurons showed 56% of putative vasopressin- (n = 41), and 37% of putative oxytocin- (n = 54) secreting neurons were activated by ET-1. Such effects normally demonstrated a short latency ( < 10 s), with a duration ranging between 10 and 300 s. In contrast, unidentified neurons in the vicinity of PVN and SON (n = 27) were unaffected by ET-1. The inability of peptides to cross the normal blood-brain barrier suggested that such effects of ET-1 result from actions of this peptide at the SFO which lacks this barrier and sends efferent neural projections to both SON and PVN. This hypothesis was tested by obtaining similar recordings from animals in which this structure was destroyed prior to experimentation. In these studies recordings from 15 putative vasopressin- and 29 putative oxytocin-secreting neurons showed that only 7% and 14%, respectively, were excited by systemic ET-1 in lesioned animals. These data show that increases in circulating levels of ET have predominantly excitatory effects on vasopressin- and oxytocin-secreting neurons in SON and PVN. The modified responsiveness of these neurons to ET-1 in SFO-lesioned animals suggests this as a likely CNS site at which this peptide acts within the central nervous system to elicit such effects.