Brooks V L, Daneshvar L, Reid I A
Department of Physiology, University of California, San Francisco 94143.
Endocrinology. 1988 Jan;122(1):97-104. doi: 10.1210/endo-122-1-97.
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)
通过检测地塞米松预处理以抑制内源性促肾上腺皮质激素（ACTH）分泌的清醒犬静脉输注血管紧张素II（AII，剂量为5、10和20 ng·kg⁻¹·min⁻¹）时ACTH在皮质醇和醛固酮反应中的作用。未处理犬静脉输注AII可使血浆皮质醇和醛固酮浓度呈剂量依赖性增加，血浆ACTH浓度也升高。地塞米松治疗使基础皮质醇浓度从1.7±0.1降至0.7±0.1μg/dl（P＜0.05），ACTH浓度从52±3降至41±4 pg/ml（P＜0.05），并消除了对所有剂量AII的皮质醇反应，表明ACTH是该反应所必需的。另一方面，地塞米松虽未显著影响基础醛固酮浓度，但降低了对最高剂量AII的醛固酮反应。进行了额外实验以确定，如果通过静脉输注合成α促肾上腺皮质激素-（1-24）（0.3 ng·kg⁻¹·min⁻¹）使ACTH浓度维持在接近对照水平，地塞米松处理犬对AII（20 ng·kg⁻¹·min⁻¹）的皮质醇和醛固酮反应是否恢复。在这组犬中，AII仍未能增加血浆皮质醇浓度；然而，醛固酮反应完全恢复。为评估升高的ACTH水平对AII类固醇生成作用的影响，用更高剂量的ACTH（0.4 ng·kg⁻¹·min⁻¹）处理犬。该剂量的ACTH使血浆皮质醇浓度从1.7±0.1升至3.5±0.8μg/dl（P＜0.05），但未显著影响血浆醛固酮浓度。在ACTH持续升高的情况下，AII（10和20 ng·kg⁻¹·min⁻¹）可增加地塞米松处理犬的血浆皮质醇浓度，尽管对10 ng·kg⁻¹·min⁻¹剂量的反应小于未处理犬。以5 ng·kg⁻¹·min⁻¹输注AII未增加血浆皮质醇浓度。相反，在ACTH水平升高时，地塞米松处理犬静脉输注AII所导致的血浆醛固酮增加未改变。最后，输注AII未改变皮质醇的清除率。总体而言，这些结果表明血浆ACTH升高是皮质醇对AII输注产生反应所必需的。（摘要截短至400字）
