VASOPRESSIN-CRF-ACTH INTERACTIONS IN THE CONSCIOUS STATE

意识状态下加压素-CRF-ACTH 的相互作用

• 批准号: 3355687
• 负责人: HERSHEL RAFF
• 金额: $ 13.83万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355687
• 关键词: adrenalectomy; adrenocorticotropic hormone; aldosterone; bioassay; blood glucose; blood osmolarity; blood pressure; catheterization; corticosteroids; corticotropin releasing factor; cortisol; denervation; dexamethasone; dogs; electrolyte balance; glucocorticoids; heart rate; hormone regulation /control mechanism; hypoglycemia; hypophysectomy; hypotension; hypothalamic pituitary axis; intraarterial administration; intravenous administration; neurohypophysis; nitroferricyanide; pituitary adrenal axis; radioimmunoassay; secretion; vagotomy; vasopressins

The proposed studies will evaluate the control of vasopressin and ACTH secretion using a well-established conscious canine model. The first project will evaluate the hypothesis that neurohypophyseal vasopressin is important in the generation of an ACTH response to those stimuli which activate neurohypophyseal vasopressin secretion into the short portal and systemic circulations. Insulin hypoglycemia without or with concomitant mild nitroprusside hypotension, which differentially activate vasopressin secretion, will be performed before and several weeks after neurohypophysectomy. In addition, intrasellar and intracarotid vasopressin infusion will determine if the effect is exerted directly at the pituitary. Finally, intravenous vasopressin infusion before and after superdiaphragmatic vagotomy will determine if vasopressin normalizes ACTH secretion in neurohypophysectomized dogs via a peripheral, possible visceral, effect. The second project will evaluate the possibility that ACTH infusion augments the subsequent ACTH response to hypertonic_ saline by increasing circulating adrenal steroids or via a non-adrenal effect. Non-glucocorticoid (aldosterone) will be evaluated as will the effect of ACTH Infusion on subsequent ACTH secretion in adrenalectomized, steroid-replaced dogs. The third project will determine if long term (7 day) physiological infusions of cortisol is effective as an inhibitor of the vasopressin response to hypertonic saline. The fourth project will determine if intravenous CRF infusion increases vasopressin secretion via a central, circulatory, or visceral effect by studying dogs after the administration of CRF antagonist into the third ventricle, after low pressure baroreceptor denervation, or after superdiaphragmatic vagotomy, respectively. It is clear that there are multiple interactions between the vasopressin and CRF-ACTH-adrenocortical control systems. These include (1) the involvement of neurohypophyseal vasopressin in ACTH secretion, (2) the negative feedback effects of adrenal steroids on vasopressin secretion, and (3) the putative role of circulatory and/or central CRF in the control of vasopressin secretion. These interactions can only be fully appreciated in terms of human health and disease if they are evaluated in a well-defined conscious animal model which allows invasive and non- invasive open and closed-loop techniques.

拟议的研究将评估血管加压素的控制， 使用良好建立的清醒犬模型的ACTH分泌。 的 第一个项目将评估神经垂体 血管加压素在促肾上腺皮质激素反应的产生中是重要的， 刺激激活神经垂体加压素分泌到 门脉和体循环短。 胰岛素低血糖，无或 伴有轻度硝普钠低血压， 激活加压素分泌，将进行前几个 在神经垂体切除术后12周。 此外，鞍内和 颈动脉内加压素灌注将决定是否发挥作用 直接在脑垂体上 最后，静脉注射加压素 在迷走神经切断术之前和之后， 血管加压素使切除神经垂体的狗的ACTH分泌正常化， 一种外围的可能是内脏的影响 第二个项目是 评估ACTH输注增加后续ACTH的可能性 通过增加循环肾上腺类固醇对高渗盐水的反应 或通过非肾上腺效应。 非糖皮质激素（醛固酮）将 评估ACTH输注对后续ACTH的影响 肾上腺切除，类固醇替代狗分泌。 第三个项目 将确定是否长期（7天）生理性输注皮质醇 作为对高渗的加压素反应的抑制剂是有效的 盐水 第四个项目将确定静脉输注CRF是否 通过中枢、循环或内脏增加加压素分泌 通过研究CRF拮抗剂给药后的犬， 低压压力感受器去神经后的第三脑室，或 迷走神经切断术后。 很明显 是加压素和 CRF-ACTH-肾上腺皮质控制系统。 其中包括（1） 神经垂体加压素参与ACTH分泌，（2） 肾上腺类固醇对加压素分泌的负反馈作用， 和（3）循环和/或中央CRF在 加压素分泌的控制。 这些相互作用只能完全 在人类健康和疾病方面受到赞赏， 一种定义明确的有意识动物模型， 侵入性开环和闭环技术。