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 (AT1; DuP 753) and CGP 42112A or PD 123177 (AT2) were used to evaluate the receptor subtype that mediates excitation of medial nTS neurons by Ang II (1 microM) in rat medulla in vitro slices. Neither losartan nor the AT2 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 microM) 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 microM, n = 12) and PD 123177 (100 microM, n = 7) failed to block excitation by Ang II in all neurons tested. Furthermore, the AT2 antagonists were ineffective in preventing Ang II-induced neuronal excitation both when they were the first antagonist tested and when they were evaluated after the neuron had recovered from AT1 receptor blockade. These studies suggest that the Ang II-induced excitation of caudal medial nTS neurons is mediated by AT1 Ang II receptors.
Barnes
K L
KL
Department of Neurosciences, Cleveland Clinic Foundation, OH 44195-5286.
McQueeney
A J
AJ
Ferrario
C M
CM
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004594:Electrophysiology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D005971:Glutamates; D007093:Imidazoles; D009842:Oligopeptides; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; D018698:Glutamic Acid; D019808:Losartan