ACTIONS OF ENDOTHELIN AT THE SUBFORNICAL ORGAN

Endothelin (ET), a potent vasoconstrictor peptide, is believed to have central sites of action and potential neurohormonal effects relating to body fluid homeostasis and blood-pressure regulation. Systemic endothelin binds to receptors at circumventricular organs and has been shown to increase plasma concentrations of vasopressin and increase the firing frequency of neurohypophysial vasopressin and oxytocin neurons. In the present study we have examined the effects of ET on blood-pressure following micro-injection into the subfornical organ (SFO). Micro-injection of 0.5 and 5.0 pmol of endothelin into SFO caused significant increases (10.1 +/- 1.1 and 10.2 +/- 2.1, respectively) in blood pressure, while lower doses were without effect. In addition, we have used single unit recording techniques to evaluate the effects of systemic ET on the activity of SFO neurons. Extracellular recordings from SFO neurons, antidromically identified as projecting to PVN, showed predominantly excitatory responses to systemic ET (21/35 cells). The data demonstrate that ET has excitatory actions on SFO neurons, and further raise the possibility that one of the functional consequences of such effects is an increase in arterial blood pressure.