Complex activation of inducible transcription factors in the brain of normotensive and spontaneously hypertensive rats following central angiotensin II administration.
The effects of intracerebroventricular (i.c.v.) injections of angiotensin II (Ang II) on the expression of inducible transcription factors (ITF) (c-Fos, FosB, c-Jun, JunB, JunD, Krox-20 and Krox-24) in the brain of conscious rats were assessed immunohistochemically using polyclonal antisera. Ang II (1, 10, 100 ng) induced after 90 min a dose-dependent expression of c-Fos, FosB, c-Jun, JunB and Krox-24, which was confined to four specific brain areas, namely the subfornical organ (SFO), median preoptic area (MnPO), paraventricular nucleus (PVN) and supraoptic nucleus (SON). In the above-mentioned regions, JunD exhibited a high basal staining which was not visibly altered by Ang II. Krox 20 was not induced by AnG II. FosB was only induced 4 h after i.c.v. injection of 100 ng Ang II in the MnPO and PVN. The Ang II-AT1 receptor antagonist, losartan, applied i.c.v. 5 min prior to Ang II (100 ng, i.c.v.) prevented the Ang II-induced ITF expression. In spontaneously hypertensive rats (SHR) but not in Wistar rats with nephrogenic hypertension due to aortic banding (WIab), the Ang II-induced expression of c-Fos, and c-Jun was enhanced in all four areas when compared to normotensive Wistar Kyoto (WKY)- and Wistar (WI) rats. The Ang II-induced expression of Krox-24 in the SFO, MnPO and PVN in SHR was also significantly increased when compared to WKY, WI and WIab rats. Our data demonstrate that a stimulation of periventricular Ang II-AT1 receptors induces a temporally and spatially highly differentiated expression pattern of ITFs restricted to four distinct regions of the forebrain involved in blood pressure regulation and body fluid homeostasis. The points to a strictly regulated expression of target genes in the respective regions. The enhanced Ang II-induced expression of ITFs in SHR compared to normotensive controls is not due to elevated blood pressure itself, since it was not observed in secondary hypertensive rats WIab. Thus, the increased sensitivity to Ang II in SHR appears to be genetically determined. The target genes regulated by Ang II-induced ITFs will have to be identified.
Department of Pharmacology, University of Kiel, Germany.
C J
CJ
Lebrun
A
A
Blume
T
T
Herdegen
E
E
Möllenhoff
T
T
Unger
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007276:Injections, Intraventricular; D011519:Proto-Oncogenes / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016335:Zinc Fingers / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D014157:Transcription Factors; D000804:Angiotensin II