Anatomical evidence that neural circuits related to the subfornical organ contain angiotensin II.

Bidirectional connections between the subfornical organ and the hypothalamus are reviewed, and emphasis is placed on recent evidence for the presence of angiotensin II in some of these pathways. Additionally, evidence is presented suggesting that this peptide may serve as a neurotransmitter or neuroendocrine factor in the efferent projections of cell groups receiving neural inputs from the subfornical organ. It appears that angiotensin II may serve as one of the chemical messengers at each link in multi-synaptic pathways related to the subfornical organ.

Subfornical organ-median preoptic connections and drinking and pressor responses to angiotensin II.

The subfornical organ (SFO) and the periventricular tissue of the anteroventral third ventricle (AV3V) have been shown to be important for the central action of circulating angiotensin. Recent anatomical findings have elucidated neural connections between the SFO and several structures within the AV3V region. The present study examined the function of fibers between the SFO and the median preoptic nucleus. Horizontal knife cuts rostral to the anterior commissure severed precommissural fibers between the SFO and the median preoptic nucleus. Cuts immediately dorsal to the anterior commissure interrupted both pre- and postcommissural connections. Rats with cuts of both sets of fibers evidenced a virtual absence of drinking responses following subcutaneous injections of angiotensin, while rats with selective cuts of precommissural fibers manifested a partial, but significant, reduction in responding. The two groups of animals showed similar attenuations in drinking responses following subcutaneous injections of hypertonic saline. Rats with cuts of both pre- and postcommissural fibers evidenced an attenuation of drinking responses elicited by centrally administered angiotensin. Pressor responses following intravenous and intraventricular angiotensin injections were not reduced specifically by the experimental knife cuts. These findings are consistent with a model that postulates that angiotensin receptors, and perhaps osmoreceptors, in the SFO send excitatory neural information to the median preoptic nucleus for the mobilization of thirst.

Localization of the anterior hypothalamic angiotensin II pressor system.

Previous studies by this laboratory have shown that an electrolytic lesion of tissue surrounding the anteroventral third cerebral ventricle (AV3V) produces pressor deficits to both intravenously (i.v.) and intracerebroventricularly (i.c.v.) administered angiotensin II (AII). These studies were designed to identify the neural substrates critical to the central AII pressor response. The AII pressor system was mapped employing a spectrum of overlapping electrolytic lesions within the medial preoptic-anterior hypothalamic area. The effect of each lesion on the pressor response to AII (i.c.v.) was tested in each animal, which was then grouped as a responder (R) or nonresponder (NR). The extent of damage produced by lesions that abolished the AII response was mapped. Bilateral destruction of tissue along the lamina terminalis (LT) either below or at the level of the anterior commissure eliminated the AII pressor response as did destruction of tissue near the margin of the preoptic and anterior hypothalamic nuclei. These data suggested that an AII pressor pathway originating in the ventral AV3V region ascends along the LT to the level of the anterior commissure and then descends through the anterior hypothalamus. The path of the descending projection through the anterior hypothalamus was ascertained by making a series of horizontal knife cuts. Transections were found that effectively eliminated the central AII pressor response without impinging upon the LT. It is concluded that the anterior hypothalamus contains an efferent pathway from the AV3V region associated with the central AII pressor response.

Periventricular preoptic-hypothalamic lesions: effects on isoproterenol-induced thirst.

Lesions of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) have been shown to block the dipsogenic properties of many experimental manipulations, including injections of angiotensin. The present study examines the ability of rats with ablations of the AV3V to initiate drinking responses following administrations of isoproterenol, a beta-adrenergic agonist which is thought to elicit drinking in part by activating the peripheral renin-angiotensin system. It was found that rats bearing lesions of the AV3V region drank significantly less across a range of doses than animals with sham lesions. When taken together with results from other studies, the present findings suggest that destroying the AV3V region inhibits the thirst-including properties of endogenous, as well as exogenous angiotensin.