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: 3355686
• 负责人: HERSHEL RAFF
• 金额: $ 13.63万
• 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/3355686
• 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.

拟议的研究将评估加压素的控制和 使用完善的有意识的犬模型来分泌 ACTH。 这 第一个项目将评估神经垂体的假设 加压素对于产生 ACTH 反应非常重要 刺激神经垂体分泌加压素 门静脉和体循环短。 胰岛素低血糖无或 伴有轻度硝普钠低血压，其差异 激活加压素分泌，将在数次之前进行 神经垂体切除术后几周。 此外，鞍内和 颈动脉内加压素输注将决定是否发挥作用 直接作用于垂体。 最后静脉输注加压素 膈上迷走神经切断术之前和之后将确定是否 加压素使神经垂体切除犬的 ACTH 分泌正常化 一种外围的、可能是内脏的效应。 第二个项目将 评估 ACTH 输注增强后续 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 或通过非肾上腺作用。 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、类固醇替代的狗的分泌。 第三个项目 将确定皮质醇是否长期（7天）生理输注 作为抗利尿激素对高渗反应的抑制剂是有效的 盐水。 第四个项目将确定是否静脉注射CRF 通过中枢、循环或内脏增加加压素分泌 通过研究狗给予 CRF 拮抗剂后的效果 第三脑室，低压压力感受器去神经支配后，或 分别在膈上迷走神经切断术后。 很明显，有 加压素和加压素之间存在多种相互作用 CRF-ACTH-肾上腺皮质控制系统。 这些包括 (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， (3) 循环和/或中枢 CRF 在 控制加压素的分泌。 这些相互作用只能充分 如果在人类健康和疾病方面进行评估，则会受到赞赏 一个明确的有意识的动物模型，允许侵入性和非 侵入性开环和闭环技术。