The role of ACTH in the cortisol and aldosterone responses to iv angiotensin II (All) infusion (5, 10, and 20 ng kg-1 min-1) in dogs was evaluated by examining the effect of All infusion in conscious dogs pretreated with dexamethasone to suppress endogenous ACTH secretion. All 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 μg/dl (P < 0.05) and the ACTH concentration from 52 ± 3 to 41 ± 4 pg/ml (P < 0.05), and abolished the cortisol response to all doses of All, 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 All was reduced. Additional experiments were performed to determine if the cortisol and aldosterone responses to All (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 αACTH-(l-24) (0.3 ng kg-1 min-1). All 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 All, 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 Mg/dl (p < 0.05), but did not significantly affect the plasma aldosterone concentration. In the presence of constant elevated levels of ACTH, All (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 All at 5 ng kg-1 min-1 did not increase the plasma cortisol concentration. In contrast, the increased plasma aldosterone produced by All infusion in dexamethasone-treated dogs was not altered in the presence of elevated ACTH levels. Finally, All 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 All infusion. The elevated ACTH levels may increase cortisol production directly or may act to increase adrenal sensitivity to a direct action of All. These results also suggest that a rise in ACTH does not contribute to the aldosterone response to All, although ACTH may be needed for normal aldosterone responsiveness to high All concentrations.
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