ANGIOTENSIN-II INDUCES A COMPLEX ACTIVATION OF TRANSCRIPTION FACTORS IN THE RAT-BRAIN - EXPRESSION OF FOS, JUN AND KROX PROTEINS

We investigated the effects of intracerebroventricular injection of an giotensin II on neuronal immediate early gene-encoded protein synthesi s in the brain of conscious rats. The expression of seven immediate ea rly gene-encoded transcription factors (c-Fos, FosB, c-Jun, JunB, JunD , Krox-20 (Egr-2) and Krox-24 (NGFI-A, Egr-1, Zif/268) was assessed si multaneously. Angiotensin II (1, 10, 100 ng) induced a dose-dependent expression of c-Fos and Krox-24 in the subfornical organ, the median p reoptic area and in the paraventricular nucleus and supraoptic nucleus of the hypothalamus, regions known to be involved in the central osmo regulatory and neuroendocrine actions of angiotensin II. FosB expressi on was induced four hours after icv injection of the highest dose of a ngiotensin II in the median preoptic area and paraventricular nucleus; c-Jun expression was restricted to the median preoptic area, subforni cal organ and paraventricular nucleus, and JunB was only induced in th e median preoptic area and subfornical organ. In these above mentioned regions, JunD exhibited a high basal staining, which was not visibly altered by angiotensin II. Krox-20 was not induced by angiotensin II. Intracerebroventricular injections of isotonic saline did not induce i mmediate early gene expression in any of the above brain areas. The an giotensin II-AT1 receptor antagonist, losartan, applied intracerbroven tricular five minutes prior to angiotensin II, prevented the angiotens in II-induced immediate early gene protein expression. Losartan alone had no effects on immediate early gene expression. Our data show for t he first time that stimulation of central periventricular angiotensin II-AT1 receptors induces a finely tuned temporospatial expression of v arious immediate early gene-encoded transcription factors in distinct regions of the forebrain involved in blood pressure regulation and bod y fluid homeostasis. Thus, angiotensin II, in addition to its short-te rm regulatory actions, can participate through these transcription fac tors in neuroplastic processes.