Heterogeneous actions of vasopressin on ANG II-sensitive neurons in the subfornical organ of rats.

The aim of this study was to investigate the effects of the antidiuretic hormone arginine vasopressin (AVP), which is released in vivo during dehydration and hypovolemia to prevent further water loss, on the activity of neurons in the subfornical organ (SFO). The SFO is a brain structure with an open blood-brain barrier and is critically involved in angiotensin II (ANG II)-dependent water intake. SFO neurons were recorded extracellularly in tissue slices of the rat brain and were tested for responsiveness to AVP and ANG II. About one-half of 159 neurons tested with an AVP concentration of 10-6 M in the superfusion medium were responsive, and approximately equal proportions were excited and inhibited. Neurons exhibiting the different response types did not differ from each other with respect to spontaneous discharge rate, latency, and duration of the response. Excitatory and inhibitory responses to AVP were dose dependent and reversible, and their threshold concentrations (10-8 to 10-9 M) were similar. Superfusion with a medium low in Ca2+ and high in Mg2+ showed that the excitatory effect is most likely direct, whereas the inhibitory effect largely depends on inhibitory synaptic interaction. About one-half of the SFO neurons excited by ANG II (10-7 M) were responsive to AVP (10-6 M), and equal proportions were inhibited and excited. Both excitatory and inhibitory AVP actions were blocked by the V1-receptor antagonist, Manning compound, and neurons responsive to AVP did not respond to the V2-receptor agonist [deamino-Cys1,d-Arg8]vasopressin. It is concluded that AVP, probably released from synaptic terminals, may increase or decrease the activity of neurons in the SFO, many of which are activated by ANG II. In contrast to previous experiments on ducks, in which the exclusively excitatory effect of the avian antidiuretic hormone arginine vasotocin on ANG II-sensitive SFO neurons correlates well with the dipsogenic effect of both peptides, a greater functional heterogeneity exists among AVP-responsive neurons in the rat SFO.