Analysis of the Role of Angiotensin II in Mediation of Adrenocorticotropin Secretion*

Abstract

It has been suggested that ACTH secretion in response to selected stimuli may be modulated by angiotensin II (AII) via direct action at the level of the corticotrope or through central actions to facilitate CRF secretion into the hypophysial-portal circulation. These hypotheses were evaluated in the present series of experiments. Our failure to observe a significant portal to peripheral plasma immunoreactive (ir) AII gradient suggested that AII does not act as a physiologically significant ACTH secretagogue at the level of the corticotrope. Central administration of synthetic AII evoked a modest dose-related stimulation of hypothalamic irCRF secretion into the portal circulation, which was reversed by the AII receptor antagonist saralasin. Activation of a known AII-positive neuronal pathway projecting from the subfornical organ (SFO) to the hypothalamic paraventricular nuclei resulted in an elevation of hypophysial-portal plasma irCRF levels and increased circulating ACTH. Pretreatment with saralasin prevented SFO stimulation-induced irCRF secretion. These observations suggest that central AII-containing pathways may participate in mediation of ACTH secretion in response to hypovolemia or hyperosmolality by facilitating irCRF secretion. Involvement of the SFO, a circumventricular organ, in this circuit is intriguing as it provides a means of monitoring peripheral irAII concentration and then converting this humoral signal into a neural signal distributed to regions regulating drinking behavior, neurohypophysial AVP secretion, and activation of the hypothalamic-pituitary-adrenal axis.

Effect of intracerebroventricular angiotensin II on body weight and food intake in adult rats

“…It is possible that chronic increases in brain ANG II had a direct effect in the PVN to downregulate CRH mRNA synthesis or increase its breakdown. Plasma corticosterone levels were not determined in the present investigation, but centrally administered ANG II has been reported to increase corticosterone via its ability to increase the secretion of vasopressin (13,20). An alternate possibility for the decreased CRH mRNA in the PVN could simply be increased negative feedback by circulating corticosterone.…”

Atrial Natriuretic Factor is Released into Hypophysial Portal Blood: Direct Evidence that Atrial Natriuretic Factor may be a Neurohormone Involved in Hypothalamic Pituitary Control

“…Thus, for example, neither we (G. Fink, I. Reid and W. F. Ganong, unpublished data) nor Plotsky et al (22) were able to detect the release of angiotensin I1 into hypophysial portal blood from intact or nephrectomized rats, in spite of the fact that there is a dense plexus of angiotensin I1 immunoreactive terminals in the ME. Similarly, we have not been able to detect the release of either cholecystokinin or substance P into rat portal blood in spite of the fact that both peptides are present in the ME as assessed by immunocytochemistry (G. Fink, A. Brar, C. Cuello, C. J. Dockray, R. C. Dow and A. Watts, unpublished data).…”

Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

“…An action of circulating RLX to activate CRF-containing neurons has not been reported previously. However, the SFO sends projections to this region of the PVN, and activation of the SFO-to-PVN pathway results in elevation of hypophyseal portal plasma CRF (44). Therefore, it is possible that some of the activated PVN neurons, not further identified in our experiments, could be CRF neurosecretory neurons.…”