Raff H, Merrill D C, Skelton M M, Brownfield M S, Cowley A W
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Endocrinology. 1988 Apr;122(4):1410-8. doi: 10.1210/endo-122-4-1410.
We examined the effect of neurohypophysectomy with and without vasopressin replacement on the ACTH response to hypotension and ovine CRF infusion and on the adrenocortical response to ACTH and angiotensin II infusion in conscious dogs. Nitroprusside hypotension (decrease in mean arterial pressure of 25 mm Hg) in the intact state resulted in large increases in plasma arginine vasopressin (pAVP; from 2.6 +/- 0.3 to 296 +/- 63 pg/ml) and ACTH (from 35 +/- 6 to 395 +/- 92 pg/ml). Neurohypophysectomy resulted in greatly attenuated pAVP (8.4 +/- 1.6 pg/ml) and ACTH (80 +/- 10 pg/ml) responses to hypotension which were not normalized by physiological low dose vasopressin replacement (6-18 pg/kg.min continuously, iv, for 2 weeks). However, acute administration of vasopressin (4-6 ng/kg.min) simultaneously with hypotension in the neurohypophysectomized (neurohypox) dog, which produced pAVP levels equivalent to the hypotensive response to intact dogs, almost completely normalized the ACTH response to hypotension (to 248 +/- 74 pg/ml). The ACTH response to 20 ng/kg.min ovine CRF, iv (from 43 +/- 8 to 268 +/- 77 pg/ml), was not attenuated by neurohypophysectomy. The cortisol responses to infusion of 0.5 and 2 ng/kg.min ACTH-(1-24), iv, were essentially normal in neurohypox dogs. However, the ACTH and aldosterone responses to 5 ng/kg.min angiotensin II infusion iv were attenuated in neurohypox dogs off AVP replacement. Histological examination revealed normal adrenal glands and anterior pituitaries in neurohypox dogs. Immunocytochemical staining for vasopressin and neurophysin revealed normal cell bodies in the paraventricular and supraoptic nuclei of the hypothalami from neurohypox dogs. However, median eminence staining for AVP and neurophysin was greatly diminished in neurohypox dogs. In summary, neurohypophysectomy 1) attenuated the ACTH response to hypotension and angiotensin II, but not to CRF, and 2) attenuated the aldosterone response to high dose angiotensin II. Furthermore, the deficit in ACTH secretion was almost completely normalized by increasing plasma AVP levels to those observed in the intact dogs. We conclude that an action of circulating pAVP increases ACTH secretion by a direct effect at the pituitary and by activating afferent input to the hypothalamus.
我们研究了去神经垂体术（伴或不伴血管加压素替代）对清醒犬促肾上腺皮质激素（ACTH）对低血压和羊促肾上腺皮质激素释放因子（CRF）输注的反应以及肾上腺皮质对ACTH和血管紧张素II输注的反应的影响。在完整状态下，硝普钠诱导的低血压（平均动脉压降低25 mmHg）导致血浆精氨酸血管加压素（pAVP；从2.6±0.3 pg/ml升至296±63 pg/ml）和ACTH（从35±6 pg/ml升至395±92 pg/ml）大幅增加。去神经垂体术导致pAVP（8.4±1.6 pg/ml）和ACTH（80±10 pg/ml）对低血压的反应显著减弱，生理性低剂量血管加压素替代（持续静脉输注6 - 18 pg/kg·min，共2周）未能使其恢复正常。然而，在去神经垂体的犬中，低血压时同时急性给予血管加压素（4 - 6 ng/kg·min），使pAVP水平达到与完整犬对低血压反应相当的水平，几乎完全使ACTH对低血压的反应恢复正常（至248±74 pg/ml）。去神经垂体术并未减弱ACTH对20 ng/kg·min羊CRF静脉输注的反应（从43±8 pg/ml升至268±77 pg/ml）。在去神经垂体的犬中，皮质醇对0.5和2 ng/kg·min促肾上腺皮质激素（1 - 24）静脉输注的反应基本正常。然而，在未进行血管加压素替代的去神经垂体犬中，ACTH和醛固酮对5 ng/kg·min血管紧张素II静脉输注的反应减弱。组织学检查显示去神经垂体犬的肾上腺和垂体前叶正常。血管加压素和神经垂体素的免疫细胞化学染色显示去神经垂体犬下丘脑室旁核和视上核的细胞体正常。然而，去神经垂体犬中血管加压素和神经垂体素的正中隆起染色明显减弱。总之，去神经垂体术1）减弱了ACTH对低血压和血管紧张素II的反应，但未减弱对CRF的反应，2）减弱了醛固酮对高剂量血管紧张素II的反应。此外，通过将血浆pAVP水平提高到完整犬中观察到的水平，ACTH分泌的缺陷几乎完全得到纠正。我们得出结论，循环中的pAVP通过对垂体的直接作用以及激活下丘脑的传入神经输入来增加ACTH分泌。
