Site at which angiotensin II acts to stimulate ACTH secretion in vivo.
To investigate the site at which angiotensin II (AII) acts to increase adrenocorticotrophic hormone (ACTH) secretion, the effects of intraventricular (IVT) or intravenous (IV) injection of the AII antagonist saralasin on the ACTH responses to IVT or IV injection of AII were examined in conscious male rats. AII does not cross the blood-brain barrier, but IVT as well as IV saralasin are known to prevent the binding of circulating AII to circumventricular organs. IV AII (0.2-200 ng) induced dose-related increases in ACTH secretion and a transient increase in the corticotrophin-releasing hormone (CRH) content of the median eminence. IVT injection of saralasin (10 micrograms) blocked the ACTH responses to IV AII. The same dose of saralasin given intravenously did not produce a comparable decrease in the ACTH response to IV AII. IVT injection of 1 and 10 ng AII increased plasma ACTH in a dose-related manner. The increase in plasma ACTH induced by IVT administration of angiotensin was not inhibited by IV infusion of saralasin (12 micrograms/kg/min). On the other hand IV infusion of this dose of saralasin abolished or reduced the ACTH response to IV injection of larger doses of AII. These data support the conclusion that circulating AII stimulates ACTH secretion by acting on the circumventricular organs to increase CRH secretion. They also suggest that AII receptors inside the blood-brain barrier as well as AII receptors in the circumventricular organs trigger increases in ACTH secretion.
Murakami
K
K
Department of Physiology, University of California, San Francisco.
Ganong
W F
WF
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D012504:Saralasin