Analysis of the role of angiotensin II in mediation of adrenocorticotropin secretion.
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.
Plotsky
P M
PM
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Sutton
S W
SW
Bruhn
T O
TO
Ferguson
A V
AV
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism; D013356:Subfornical Organ / Q000502:physiology
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone