Receptor subtype that mediates the neuronal effects of angiotensin ii in the rat dorsal medulla

We have shown previously that many neurons in the caudal medial nucleus tractus solitarii (nTS) are excited by angiotensin (Ang) II. The selective Ang II receptor antagonists losartan (AT 1; DuP 753) and CGP 42112A or PD 123177 (AT 2) were used to evaluate the receptor subtype that mediates excitation of medial nTS neurons by Ang II (1 μM) in rat medulla in vitro slices. Neither losartan nor the AT 2 antagonists altered the baseline firing of either Ang II-sensitive or Ang II-unresponsive neurons. However, in six cells with low-frequency spontaneous activity that remained above baseline after excitation by Ang II, subsequent administration of losartan reversed the firing pattern to the initial low-frequency activity. Losartan (10 μM) blocked the excitation by Ang II in 29 medial nTS neurons. The Ang II-induced excitation recovered from Type I blockade in 1 h. In contrast, both CGP 42112A (10 and 100 μM, n = 12) and PD 123177 (100 μM, n = 7) failed to block excitation by Ang II in all neurons tested. Furthermore, the AT 2 antagonists were ineffective in preventing Ang Il-induced neuronal excitation both when they were the first antagonist tested and when they were evaluated after the neuron had recovered from AT 1 receptor blockade. These studies suggest that the Ang II-induced excitation of caudal medial nTS neurons is mediated by AT 1 Ang II receptors.