AUTORADIOGRAPHIC IDENTIFICATION OF BRAIN ANGIOTENSIN-IV BINDING-SITESAND DIFFERENTIAL C-FOS EXPRESSION FOLLOWING INTRACEREBROVENTRICULAR INJECTION OF ANGIOTENSIN-II AND ANGIOTENSIN-IV IN RATS

A unique angiotensin binding site specific for the hexapeptide, angiot ensin II(3-8) (AngIV), has been previously reported by our laboratory in the guinea pig brain and is presently described in the rat brain. T his angiotensin receptor subtype has been termed AT(4) and is prominen tly distributed in cerebral cortex, piriform cortex, hippocampus, habe nulae, colliculi, septum, periaqueductal gray, several thalamic nuclei , the arcuate nucleus of the hypothalamus and cerebellum. In the secon d part of the present investigation, separate groups of rats received i.c.v. injections of angiotensin II (AngII), AngIV or artificial cereb rospinal fluid (aCSF) and were euthanized 2 h later for the purpose of evaluating for brain c-Fos expression. After i.c.v.-injected AngIV, F os-like immunoreactivity was present in the hippocampus and piriform c ortex. This immunoreactivity was unaffected by i.c.v. pretreatment wit h the AT(1) angiotensin receptor antagonist DuP 753 (losartan) or the AT(2) receptor ligand PD123177 but was blocked by the AT(4) angiotensi n receptor antagonist, divalanal-AngIV. I.c.v. injection of AngII resu lted in Fos-like immunoreactivity in the dorsal third and lateral vent ricles, subfornical organ, lateral hypothalamus and amygdala. Pretreat ment with losartan or PD123177 significantly interfered with this AngI I-induced immunoreactivity while divalanal-AngIV did not. These result s indicate that in both guinea pig and rat brains the AT(4) receptor h as a distribution different than that previously reported for AT(1) an d AT(2) receptor subtypes. The c-Fos expression results suggest that d ifferent brain neuronal pathways are activated by i.c.v. injection of AngII and AngIV.