Spinedi E, Negro-Vilar A
Life Sci. 1984 Feb 20;34(8):721-9. doi: 10.1016/0024-3205(84)90379-5.
Recent studies from our laboratory indicate a primary central site of action of Angiotensin II (AII) to release ACTH. The present studies were designed to test whether AII is able to release ACTH in vivo in a similar fashion in intact, cannulated, freely moving Long-Evans (LE) or in vasopressin (AVP)-deficient, Brattleboro (DI) female rats. The in vivo response to AII was compared with that elicited by synthetic CRF. AII injected i.v. (0.4 or 2 micrograms/100 g BW) induced a significant, dose-related increase in plasma ACTH values 5 and 15 min after injection, in both LE and DI rats. CRF given to LE and DI rats at 0.4 micrograms/100 g BW elicited a larger increase in ACTH plasma values than a similar dose of AII, 5 or 15 min after the injection. Moreover, ACTH levels after CRF in DI rats were significantly greater than those obtained in LE controls. In vitro studies using dispersed anterior pituitary cells indicate that the response of cells from either LE or DI rats to AII or AVP (both at 10(-9) and 10(-8)M) was similar. Cells from DI donors were hyperresponsive to CRF (2 X 10(-11) and 10(-10)M) in terms of ACTH release when compared with the response of cells from LE rats. The present results suggest that the presence of AVP is not essential to mediate the central response to AII and that AII may act centrally to stimulate CRF release from the hypothalamus in vivo, which would then enhance ACTH output. The results in the DI rat indicate that the increased response to CRF may be an important compensatory mechanism involved in the regulation of adrenocortical function in the DI rat.
我们实验室最近的研究表明，血管紧张素II（AII）释放促肾上腺皮质激素（ACTH）的主要作用部位在中枢。本研究旨在测试AII在完整、插管、自由活动的长-伊文斯（LE）大鼠或血管加压素（AVP）缺乏的布氏（DI）雌性大鼠体内，是否能够以类似的方式释放ACTH。将AII的体内反应与合成促肾上腺皮质激素释放因子（CRF）引发的反应进行比较。静脉注射AII（0.4或2微克/100克体重）后5分钟和15分钟，LE和DI大鼠的血浆ACTH值均出现显著的、与剂量相关的升高。以0.4微克/100克体重给LE和DI大鼠注射CRF后，在注射后5分钟或15分钟，其血浆ACTH值的升高幅度大于相同剂量的AII。此外，DI大鼠注射CRF后的ACTH水平显著高于LE对照大鼠。使用分散的垂体前叶细胞进行的体外研究表明，LE或DI大鼠的细胞对AII或AVP（均为10^(-9)和10^(-8)M）的反应相似。与LE大鼠的细胞反应相比，DI供体的细胞在ACTH释放方面对CRF（2×10^(-11)和10^(-10)M）反应更强。目前的结果表明，AVP的存在对于介导对AII的中枢反应并非必不可少，并且AII可能在体内通过中枢作用刺激下丘脑释放CRF，进而增强ACTH的分泌。DI大鼠的结果表明，对CRF反应增强可能是DI大鼠肾上腺皮质功能调节中一种重要的代偿机制。
