Fos protein is required for the re-expression of angiotensin II type 1 receptors in the nucleus tractus solitarii after baroreceptor activation in the rat

We evaluated in Sprague-Dawley rats the hypothesis that Fos protein induced by baroreceptor activation in the nucleus tractus solitarii participates i n transcriptional regulation of the expression of angiotensin receptor gene s. Reverse transcription-polymerase chain reaction revealed that barorecept or activation elicited by sustained hypertension resulted in a transient de crease in angiotensin II subtype 1, but not subtype 2, receptor messenger R NA, in the dorsomedial medulla, including the nucleus tractus solitarii. Th ere was subsequently a transitory reduction in the presser response elicite d by microinjection bilaterally of angiotensin II (40 pmol) into the nucleu s tractus solitarii, followed by an increase in c-fos messenger RNA and Fos immunoreactivity at the same nucleus. Both the re-expression of angiotensi n II subtype 1 receptor messenger RNA and restoration of pressor response t o angiotensin II after baroreceptor activation were significantly blunted b y bilateral application into the nucleus tractus solitarii of an antisense oligonucleotide (50 pmol) that targets against the initiation codon of c-fo s messenger RNA. Control pretreatment with the corresponding sense oligonuc leotide (50 pmol). or an antisense c-fos oligonucleotide that targets again st a different portion of the coding sequence of the c-fos messenger RNA (5 0 pmol), was ineffective. At the receptor level. the angiotensin II-induced presser response was antagonized by the subtype I receptor antagonist losa rtan (1.6 nmol), but not by the subtype 2 receptor antagonist PD-123319 (1. 6 nmol). These findings suggest that sustained hypertension down-regulates angiotens in II subtype 1 receptors at both meseenger RNA and functional expression l evels in the nucleus tractus solitarii. Furthermore, Fos protein induced in the nucleus tractus solitarii by baroreceptor activation may play a permis sive role in the transcriptional regulation of the re-expression of this su btype of angiotensin receptors. (C) 2001 IBRO. Published by Elsevier Scienc e Ltd. All rights reserved.