VASOPRESSIN-CRF-ACTH INTERACTIONS IN THE CONSCIOUS STATE

拟议的研究将评估加压素的控制和 利用已建立的清醒犬模型分泌ACTH。这个 第一个项目将评估神经垂体素的假设 加压素在产生ACTH反应中起重要作用 刺激神经垂体后叶加压素分泌进入 门脉和全身循环较短。无或无胰岛素低血糖 伴有轻度硝普钠低血压，这与 激活后叶加压素的分泌，之前会做几次 神经垂体切除术后几周。此外，鞍内和 颈动脉内注射加压素将决定这一效应是否发挥 直接对准脑下垂体部。最后，静脉滴注加压素 隔肌上迷走神经切断术前后将决定是否 加压素通过以下途径调节神经垂体切除犬ACTH的分泌 一种外在的，可能是内脏的影响。第二个项目将 评估ACTH输注增加后续ACTH的可能性 循环肾上腺类固醇激素增加对高渗盐水的反应 或者通过非肾上腺效应。非糖皮质激素(醛固酮)将是 ACTH输注对后续ACTH影响的评估 肾上腺切除、类固醇替代犬的分泌物。第三个项目 将决定是否长期(7天)生理输注皮质醇 是一种有效的血管加压素对高渗反应的抑制剂 生理盐水。第四个项目将确定静脉注射CRF是否 通过中枢、循环或内脏增加加压素的分泌 犬应用促肾上腺皮质激素释放激素拮抗剂后的研究 第三脑室，在低压压力感受器去神经后，或 分别于隔肌上迷走神经切断术后。很明显，在那里 是加压素和加压素的多重相互作用 CRF-ACTH-肾上腺皮质控制系统。这些措施包括(1) 神经垂体加压素参与促肾上腺皮质激素分泌，(2) 肾上腺类固醇对加压素分泌的负反馈作用 和(3)循环和/或中枢CRF在 控制加压素的分泌。这些相互作用只能完全 在人类健康和疾病方面受到赞赏，如果它们被评估为 一种定义明确的清醒动物模型，允许有侵入性和非侵入性 侵入性的开环和闭环技术。

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.