Right adrenal and various cardiovascular responses to an intra-aortic infusion of calcitonin gene-related peptide (CGRP; 4 micrograms min-1) have been investigated in the presence and absence of exogenous adrenocorticotrophin ACTH1-24 (2 or 5 ng min-1 kg-1, I.V.). The adrenal clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3-7 days previously. 2. At the higher dose (5 ng min-1 kg-1) the I.V. infusion of ACTH raised mean plasma ACTH concentration by about 1000 pg ml-1 and mean right adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal function, other than to produce moderate adrenal vasodilatation. In contrast, in the absence of exogenous ACTH, the same dose of CGRP produced a substantial rise in cortisol output, which rose steadily to a peak mean value of 409 +/- 31 pg min-1 kg-1 at 10 min. It also significantly inhibited the release of free, but not of total, met5-enkephalin-like immunoreactivity from the gland (P less than 0.001) together with a significantly greater fall in adrenal vascular resistance (P less than 0.001). 3. At the lower dose of ACTH (2 ng min-1 kg-1, I.V.) CGRP raised mean plasma cortisol output from 314 +/- 31 to 486 +/- 44 ng min-1 kg-1 (P less than 0.01) and this effect was not attributable to an increase in the adrenal presentation rate of ACTH. 4. It is concluded that this peptide exerts a steroidogenic action on the adrenal cortex which is manifest in the absence of exogenous ACTH in the functionally hypophysectomized calf.
摘要
在有和没有外源性促肾上腺皮质激素ACTH1 - 24(2或5 ng min⁻¹ kg⁻¹,静脉注射)的情况下,研究了右肾上腺及各种心血管对主动脉内注入降钙素基因相关肽(CGRP;4微克min⁻¹)的反应。在有意识的犊牛中采用肾上腺钳夹技术,这些犊牛的垂体柄在3 - 7天前已被烧灼。2. 在较高剂量(5 ng min⁻¹ kg⁻¹)时,静脉注射ACTH使平均血浆ACTH浓度升高约1000 pg ml⁻¹,右肾上腺皮质醇平均输出量升高约750 ng min⁻¹ kg⁻¹。在这些条件下,主动脉内注入CGRP对肾上腺皮质醇输出量没有明显影响,仅产生中度的肾上腺血管舒张。相比之下,在没有外源性ACTH的情况下,相同剂量的CGRP使皮质醇输出量大幅增加,在10分钟时稳定上升至峰值平均值409±31 pg min⁻¹ kg⁻¹。它还显著抑制了腺体中游离的(而非总)甲硫氨酸脑啡肽样免疫反应性的释放(P<0.001),同时肾上腺血管阻力显著下降(P<0.001)。3. 在较低剂量的ACTH(2 ng min⁻¹ kg⁻¹,静脉注射)时,CGRP使平均血浆皮质醇输出量从314±31升高至486±44 ng min⁻¹ kg⁻¹(P<0.01),且这种作用并非归因于ACTH肾上腺呈现率的增加。4. 得出的结论是,在功能上垂体切除的犊牛中,在没有外源性ACTH的情况下,这种肽对肾上腺皮质发挥类固醇生成作用。