The role of adrenocorticotropin in the cortisol and aldosterone responses to angiotensin II in conscious dogs

Abstract

The role of ACTH in the cortisol and aldosterone responses to iv angiotensin II (AII) infusion, (5, 10, and 20 ng kg-1 min-1) in dogs was evaluated by examining the effect of AII infusion in conscious dogs pretreated with dexamethasone to suppress endogenous ACTH secretion. AII infusion in untreated dogs produced dose-related increases in plasma cortisol and aldosterone concentrations. The plasma ACTH concentration also increased. Dexamethasone treatment lowered the basal cortisol concentration from 1.7 +/- 0.1 to 0.7 +/- 0.1 micrograms/dl (P less than 0.05) and the ACTH concentration from 52 +/- 3 to 41 +/- 4 pg/ml (P less than 0.05), and abolished the cortisol response to all doses of AII, indicating that ACTH was necessary for the response. On the other hand, the basal aldosterone concentration was not significantly affected by dexamethasone, although the aldosterone response to the highest dose of AII was reduced. Additional experiments were performed to determine if the cortisol and aldosterone responses to AII (20 ng kg-1 min-1) in dexamethasone-treated dogs are restored if the ACTH concentration is maintained near control levels by iv infusion of synthetic alpha ACTH-(1-24) (0.3 ng kg-1 min-1). AII still failed to increase the plasma cortisol concentration in this group of dogs; however, the aldosterone response was fully restored. To evaluate the effect of elevated ACTH levels on the steroidogenic effects of AII, dogs were treated with dexamethasone and a higher dose of ACTH (0.4 ng kg-1 min-1). This dose of ACTH increased the plasma cortisol concentration from 1.7 +/- 0.1 to 3.5 +/- 0.8 micrograms/dl (P less than 0.05), but did not significantly affect the plasma aldosterone concentration. In the presence of constant elevated levels of ACTH, AII (10 and 20 ng kg-1 min-1) increased the plasma cortisol concentration in dexamethasone-treated dogs, although the response to the 10 ng kg-1 min-1 dose was smaller than the response in untreated dogs. Infusion of AII at 5 ng kg-1 min-1 did not increase the plasma cortisol concentration. In contrast, the increased plasma aldosterone produced by AII infusion in dexamethasone-treated dogs was not altered in the presence of elevated ACTH levels. Finally, AII infusion did not alter the clearance of cortisol. Collectively, these results demonstrate that an increase in plasma ACTH is necessary for the cortisol response to AII infusion.(ABSTRACT TRUNCATED AT 400 WORDS)