Direct regulation of hypothalamic corticotropin-releasing-hormone neurons by angiotensin II

The possible role of angiotensin II (AII) in the control of the hypothalamic-pituitary-adrenal (HPA) axis was studied in the rat by examining the regulation and cellular localization of AII receptors in the paraventricular nucleus (PVN) of the hypothalamus and the effect of AII on corticotropin-releasing hormone (CRH) and vasopressin (VP) mRNA levels. In situ hybridization studies using cRNA 35S-labelled probes showed that while type 1 AII receptor (AT1) mRNA levels were high in the periventricular and parvicellular pars of the PVN, only very low levels were present in the magnocellular pars. A similar distribution of AT1 receptor binding in the periventricular, parvicellular and magnocellular divisions of the PVN was observed in autoradiographic studies in hypothalamic sections labelled with 125I[Sar1,Ile8]AII. In addition, AII receptor binding was clearly evident in nerve fibers adjacent to the PVN. Double-labelling hybridization using digoxigenin-labelled CRH, VP and oxytocin probes and 35S-labelled AT1 receptor cRNA probes showed AT1 receptor mRNA in cells stained for CRH mRNA, but not in VP or oxytocin cells. Four hours after a single intracerebroventricular (i.c.v.) injection of 50 ng AII in conscious rats, CRH mRNA levels in the PVN were increased by 43%, similar to the increases observed following acute stress by intraperitoneal (i.p.) injection of 1.5 M NaCl (76%). On the other hand, while i.p. hypertonic saline injection increased VP mRNA levels by 29% in the PVN and by 32% in the supraoptic nucleus, i.c.v. AII injection had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)