Systemic Angiotensin Acts at the Subfornical Organ to Control the Activity of Paraventricular Nucleus Neurons with Identified Projections to the Median Eminence

Abstract

The present studies were carried out to investigate the mechanisms through which systemic angiotensin II (AII) acts within the central nervous system to influence the release of anterior pituitary hormones in the Sprague-Dawley rat. In particular, these studies have examined the role of the subfornical organ (SFO) as an essential structure mediating these responses. Extracellular single-unit recordings were obtained from 199 paraventricular nucleus (PVN) neurons anti-dromically identified as projecting to the median eminence. Different groups of these neurons were tested for the effects of either electrical stimulation in the SFO (n = 87) or systemic AII administration in intact (n = 49) and SFO-lesioned (n = 25) animals. Of cells tested with SFO stimulation 45% were excited, 16% inhibited, and the remainder unaffected. Neurons which were excited were primarily located just medial to the magnocellular neurons in the region where the majority of corticotropin-releasing hormone immunoreactive cells are found. In contrast, inhibitory responses were observed in cells located in the dorsal medial PVN, a region containing thyrotropin-releasing hormone, somatostatin, and dopamine PVN-median eminence neurons. Following systemic AII 42% of cells tested showed increased activity specific to the effects of this peptide, and 20% showed alterations in activity associated with the cardiovascular changes induced by AII. In contrast, following SFO lesion only 8% of neurons tested showed specific excitatory responses to AII. In order to test the hypothesis that systemic AII may activate this excitatory SFO to PVN pathway, a further group of 35 neurons were tested with both SFO stimulation and AII. Excitatory responses to AII were observed in 13 of these cells, each of which was also excited by SFO stimulation. These studies describe mechanisms through which the central nervous system may sense peripheral concentrations of peptide hormones and modulate the activity of neural pathways which in turn influence the activity of PVN neurons which control the secretion of anterior pituitary hormones.

Chronic angiotensin II infusion attenuates the renal sympathoinhibitory response to acute volume expansion

“…Neurons in the CVOs, notably the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT), not only sense circulating peptides like ANG II (3,14) but also send ANG II-immunoreactive efferent projections to the PVN where neurons express a high concentration of ANG II AT 1 receptors (23,29). Electrophysiological studies demonstrate that ANG II can increase PVN unit discharge when applied either directly within the SFO or when given systemically (1,15). Together, available evidence indicates that ANG II is a likely neurotransmitter released from SFO terminals within the PVN (22,41).…”

Angiotensin II receptors in paraventricular nucleus, subfornical organ, and pituitary gland of hypophysectomized, adrenalectomized, and vasopressin-deficient rats.

“…The subfornical organ sends a dense, angiotensin II-containing projection to the paraventricular nucleus (14), and angiotensin II-binding sites are concentrated along this pathway (15). It seems likely, therefore, that subfornical organ-paraventricular nucleus projection is at least one source for angiotensin II that binds to angiotensin receptors in the paraventricular nucleus and that this connection mediates the effects of circulating angiotensin II in the control of pituitary function (9,12).Angiotensin receptors are increased after repeated stress in the paraventricular nucleus and subfornical organ (16) and after dehydration in the subfornical organ (17). Increased concentration of circulating angiotensin II might upregulate its own receptors in stress and dehydration by a mechanism similar to that described for peripheral angiotensin receptors (18).…”

“…Vasopressin release is increased by central (10) and perhaps also by peripheral (11) administration of angiotensin II. Peripheral angiotensin II administration stimulates ACTH release from the anterior pituitary gland (12), but this effect may be mediated through the brain angiotensin II system: circulating angiotensin II may bind to receptors in circumventricular organs and stimulate the brain angiotensin II system, which leads to increased ACTH release probably through the stimulation of corticotropinreleasing hormone (CRH) secretion from the hypothalamus (9,12).…”

Adenoviral inhibition of AT1a receptors in the paraventricular nucleus inhibits acute increases in mean arterial blood pressure in the rat

“…Electrophysiological studies have confirmed that circulating ANG II affects sympathetic premotor neurons in the PVN, some of which are associated with cardiovascular changes induced by ANG II locally (15). These PVN premotor neurons project to the RVLM, an area that is involved in cardiovascular regulation (11,23,26,30,35,40).…”