CHRONIC STRESS & SODIUM EFFECTS ON HYPERTENSION

慢性压力

• 批准号: 3357249
• 负责人: JAYLAN S TURKKAN
• 金额: $ 11.31万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3357249
• 关键词: Cercopithecidae; alpha adrenergic agent; angiotensin /renin /aldosterone hypertension; antihypertensive agents; atrial natriuretic peptide; behavior test; behavioral medicine; beta antiadrenergic agent; blood pressure; calcium channel blockers; cardiovascular pharmacology; catecholamines; chlorothiazide; clonidine; computer data analysis; desoxycorticosterone; dietary mineral; diuretics; dosage; eating; enzyme inhibitors; escape reaction; hormone regulation /control mechanism; hypertension; hypothalamic pituitary axis; kidney pharmacology; magnetic resonance imaging; neuroendocrine system; nifedipine; propranolol; renal hypertension; renin; salt intake; saluresis; saralasin; sodium; stress; sympathetic nervous system; ventricular hypertrophy; water drinking behavior

The proposed studies investigate the combined effects of two variables behavior stress and excess sodium intake- that have been highly implicated in the loss of regulatory control of blood pressure (BP) leading to hypertension. The project will study normotensive baboons before, during and after six months of exposure to daily behavioral stress sessions combined with daily ingestion of excess dietary sodium. Controls will receive stress only. Additionally, baboons with one renal artery constricted will be exposed to stress without excess sodium. Salt will be administered by training subjects to ingest hypertonic saline (8.6 mEq Na/kg/day) in juice. Behavioral stress will make use of two known effective procedures, where previously trained behaviors are no longer successful in obtaining food (extinction), and, where food acquisition behaviors produce a mild electric shock (conflict). Both stress components will occur unpredictably during portions of daily experimental sessions. Stage 1 will assess, BP, heart rate, and levels of the neuroendocrine substances catecholamines and metabolites, renin activity and aldosterone, 17-hydroxycorticosteroids, atrial natriuretic peptide, and other regulatory and electrolyte levels. Left ventricular mass may increase after six months of BP elevation due to the stress sodium combination; this will be assessed with use of nuclear magnetic resonance (MRI) imaging of the heart. If the stress and sodium combination in Stage 1 chronically increases BP in healthy baboons by at least 15 mmHg, and if stress exacerbates the already existing hypertension in the renovascular monkeys, stage 2 will include study of: the relative contributions of given amounts of salt and/or stress to the hypertension; means to enhance the salt-stress effect, including manipulations of predictability and controllability of the behavioral stress schedule; and, pathophysiologic mechanisms inferred from relative responsiveness to antihypertensive treatments and from blood levels of neuroendocrine substances. If the Stage 1 data show that the salt-stress combination does not chronically increase BP in the baboon, then Stage 2 will assess whether the addition of deoxycorticosterone acetate (DOCA) will enhance the stress-sodium combination, and, will enhance the effects of stress in renovascular hypertensive baboons. Those parameters found to be optimal in producing BP elevations will be used in a new cohort of baboons in Years 3-5. Throughout, MRI imaging of the heart will be repeated 3/year for experimental and control subjects.

拟议的研究研究了两个 变量行为压力和摄入过量的钠 高度涉及血液调节控制的丧失 压力（BP）导致高血压。 该项目将研究 六个月之前，之中和之后，狒狒正常 暴露于每日行为压力会话与每日相结合 摄入过量饮食钠。 控件将受到压力 仅有的。 另外，一个肾动脉收缩的狒狒将 面临压力而不会过多的钠。 盐会 通过训练受试者进行摄入高渗盐水的管理（8.6 果汁中的meq na/kg/day）。 行为压力将使用两个 已知的有效程序，以前训练的行为 不再成功获得食物（灭绝），也不再 食物获取行为会产生轻度的电击 （冲突）。 这两种压力成分将在 每日实验会议的一部分。 第1阶段将评估BP， 心率和神经内分泌物质的水平 儿茶酚胺和代谢物，肾素活性和醛固酮， 17-羟基皮质类固醇，心房纳地肽和其他 调节和电解质水平。 左心室质量可能 由于压力钠，BP升高六个月后增加 组合;这将通过使用核磁来评估 共鸣（MRI）心脏成像。 如果压力和钠 第1阶段的组合长期增加健康的BP 狒狒的至少15 mmHg，如果压力加剧了 肾脏猴子已经存在的高血压，阶段 2将包括：给定的相对贡献的研究 高血压的盐分和/或压力；意味着 增强盐压力效果，包括 行为应力的可预测性和可控性 日程;而且，从 对降压治疗的相对反应 神经内分泌物质的血液水平。 如果阶段1数据 证明盐压力组合不会长期存在 增加狒狒的BP，然后第2阶段将评估是否是否 乙酸脱氧核酮（DOCA）的添加将增强 应力 - 钠组合，并将增强压力的影响 在肾血管高血压狒狒中。 这些参数发现 在新的队列中将使用最佳的BP高程 3 - 5年的狒狒。 在整个过程中，心脏的MRI成像 对于实验和对照对象，将重复3/年。