Effect of repetitive icv injections of ANG II on c-Fos and AT(1)-receptor expression in the rat brain

ANG II has been implicated in neuroplastic processes via stimulation of ind ucible transcription factors (ITF) in the brain. In the present study, we i nvestigated the effects of acute vs. repetitive once daily intracerebrovent ricular injections of ANG II for 7 days on the expression of ITF and consti tutive transcription factor (CTF) and the AT(1) receptor in the median preo ptic area (MnPO), the subfornical organ (SFO), and the hypothalamic paraven tricular (PVN) and supraoptic nuclei (SON). After repetitive injections, th e expression of c-Fos declined by similar to 50% in MnPO, SFO, PVN, and SON compared with controls injected once. The desensitization of c-Fos occurre d on the transcriptional level as shown in the SON by RT-PCR. Apart from a novel expression of c-Jun in the SON, the ITF c-Jun, JunB, JunD, and Krox-2 4 did not change after repetitive stimulation. Neither were the CTF, calciu m response element binding protein, activating transcription factor 2, and serum response factor altered after repetitive vs. single injections of ANG II. The AT(1) receptor was coexpressed with c-Fos/c-Jun. Immunohistochemic al stainings suggest an increase in AT(1) receptor number in MnPO, SFO, PVN , and SON on chronic stimulation compared with once-injected controls. Thes e findings demonstrate that repetitive periventricular stimulation with ANG II essentially alters the expression of transcription factors compared wit h acute stimulation and suggest c-Fos and c-Jun as major intermediates of t he AT(1) receptor transcription.