Studying the central actions of angiotensin using the expression of immediate-early genes: expectations and limitations

Abstract

Intracerebral infusions of angiotensin II (Ang-II) elicit a widespread but discrete expression of c- fos (and other immediate-early genes: IEGs) in the basal forebrain and brainstem. This has given us a new approach to the study of the central actions of Ang-II (and other peptides). It is unlikely that the dipsogenic response to Ang-II is directly related to c- fos expression in the AV3V, since the onset of behaviour occurs much before that of gene expression, and suppression of drinking by preloading rats with water does not alter Ang-II-induced c- fos in this part of the brain. Whether endocrine or cardiovascular actions are directly related to c- fos needs to be established. Water intake inhibits c- fos in the SON and PVN; whether this is a direct interaction between Ang-II and altered osmolality on magnocellular neurons or a secondary event of an action elsewhere (e.g., in the AV3V) remains uncertain. AV3V (median preoptic nucleus) lesions also inhibit Ang-II-evoked c- fos in the SON and PVN as well as in brainstem Ang-II sensitive sites such as the NTS and parabrachial nucleus, suggesting that the AV3V may be a nodal site for the distributed action of Ang-II. The rapid dipsogenic effects of Ang-II may involve glutamate receptors, since i.c.v. dizocilpine (an NMDA open channel antagonist) reduces both drinking and c- fos expression after i.c.v. Ang-II. This relatively new IEG technique acts as an anatomical and temporally specific marker of neuronal response to Ang-II, and has already added to knowledge about the central actions of Ang-II at the level of the neuron. Combining this approach with other methods allows cellular events in the brain to be related to the functional effects of Ang-II and its adaptive role in regulating water and salt metabolism.