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The present studies utilized the in vitro slice preparation of the canine dorsomedial medulla, which we have recently developed, to obtain direct evidence for the effects of angiotensin II (Ang II) on the activity of single neurons in this region. Horizontally oriented slices (300 micron) containing the area postrema, nucleus tractus solitarii (NTS), and dorsal motor nucleus of the vagus were perifused with oxygenated artificial cerebrospinal fluid. The effects of microdrop application of Ang II and its antagonist [Sar1,Thr8]Ang II on spontaneous firing rate were determined in 27 extracellularly recorded neurons. Ang II substantially increased the firing rate of 13 neurons located in the medial NTS, but it did not alter the spontaneous activity of the remaining 14 neurons. In most cases Ang II elicited a slowly developing, prolonged excitatory response. The effects of both Ang II and [Sar1,Thr8]Ang II were tested in 13 neurons. [Sar1,Thr8]Ang II produced a short latency, brief excitation in three neurons, marked inhibition of spontaneous firing in two cells, and no effect on the other eight neurons. Administration of [Sar1,Thr8]Ang II blocked the excitatory effects of subsequent administration of Ang II in three neurons. To our knowledge, these observations provide the first evidence for direct actions of both Ang II and [Sar1,Thr8]Ang II on neurons in the canine NTS and for the specificity of the neuronal effects of Ang II as documented by blockade of the excitatory response to Ang II by [Sar1,Thr8]Ang II.

Neuronal responses to angiotensin II in the in vitro slice from the canine medulla.