Submitted on September 30, 2004
Accepted on May 3, 2005
Ang III induces the expression of inducible transcription factors of the AP-1 and Krox families in the rat brain
Annegret Blume1*, Christian Undeutsch1, Yi Zhao1, Elena Kaschina2, Juraj Culman1, and Thomas Unger2
1 Institute of Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts-University of Kiel, Kiel, Schleswig-Holstein, Germany
2 Center for Cardiovascular Research (CCR), Campus Charite-Mitte, Humboldt University, Berlin, Germany
* To whom correspondence should be addressed. E-mail: annegret.blume{at}biologie.uni-regensburg.de.
Besides rapid responses comprising increases in blood pressure, drinking and stimulation of natriuresis, angiotensin II (Ang II) induces the expression of
transcription factors (TF) in the central nervous system. The Ang II metabolite Ang III (Ang 2-8) has been demonstrated to exert similar physiological effects as Ang II. We aimed to determine 1. whether Ang III induces TF expression in the brain; 2. which angiotensin (AT) receptor subtype is involved and 3. whether the two peptides, Ang II and Ang III, differ in their efficacy to stimulate TF expression. Ang II (100 pmol), Ang III (100 pmol) or vehicle were injected into the lateral brain ventricle of conscious rats alone or in combination with the AT1 receptor antagonist losartan (10 nmol), the AT2
receptor antagonist PD123319 (5 nmol) or the aminopeptidase inhibitor, amastatin (10 nmol). Similarly to Ang II, Ang III induced the expression of c-Fos, c-Jun and Krox 24 in four brain regions, the subfornical organ, median preoptic area, paraventricular nucleus and supraoptic nucleus of the hypothalamus with the same efficacy. This effect was AT1 receptor-mediated. Pretreatment with amastatin reduced the expression of TF in response to Ang II, indicating that this expression is partly mediated by Ang III. Interestingly, the AT2 receptor antagonist, PD 123319, alone slightly enhanced the expression of c-Fos, c-Jun and Krox 24 in different populations of neurons of the paraventricular nucleus. These data indicate that different populations of neurons in the paraventricular nucleus are tonically inhibited by AT2 receptors under physiological conditions.
