CARDIOVASCULAR PHARMACOLOGY OF ATRIAL NATRIURETIC FACTOR

心房钠尿因子的心血管药理学

• 批准号: 3352435
• 负责人: ALAN S HOLLISTER
• 金额: $ 16.58万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3352435
• 关键词: atrial natriuretic peptide; autonomic reflex; blood volume; body fluid osmolarity; cardiovascular pharmacology; dietary mineral; diuretics; heart catheterization; hormone regulation /control mechanism; human tissue; hypertension; peptide hormone; radioimmunoassay; vasoconstrictors; vasomotion

Atrial natriuretic factor (ANF) is a polypeptide hormone which exhibits potent natriuretic, diuretic and vascular smooth muscle- relaxing actions. Animal studies indicate that mechanical or volume-induced atrial stretch, sodium loading, and vasopressor agonists stimulate the release of ANF. Bolus infusions cause a brief fall in blood pressure which precedes the diuresis and natriuresis stimulated by ANF. Overall, the studies in animals suggest that ANF functions as a volume-regulatory hormone in concert with the actions of antidiuretic hormone and aldosterone. To date, human studies with ANF have shown diuretic and natriuretic actions of single bolus infusions of ANF, with no studies of the mechanisms and stimuli which regulate release of ANF. In our preliminary studies, a high salt diet promoted a weight gain-related increase in plasma ANF concentrations. Upright posture provoked a fall in plasma ANF, suggesting that right sided filling pressures regulate ANF release. In cardiac catheterization studies we found a marked increase in plasma ANF concentrations in the right atrium, and the ANF levels correlated positively with atrial pressure. Elevation of the legs increased atrial pressure and stimulated an increase in secretion rate of ANF across the heart. Altogether, our studies support the hypothesis that ANF may function in humans as a volume- regulatory hormone whose plasma concentration is modulated by atrial pressure. The studies outlined in this proposal are designed to 1) determine the physiological, hormonal and volume stimuli which regulate human plasma ANF concentrations, 2) characterize the cardiovascular actions of ANF in normal subjects, and 3) elucidate the physiological regulation and cardiovascular actions of ANF in patients with essential hypertension. We plan to systematically manipulate atrial pressure, test a series of vasoactive agonists and manipulate plasma volume and osmolarity to determine the contribution of each of these stimuli to the regulation of plasma ANF concentration. Second, using bolus and sustained infusions of synthetic ANF we will determine its cardiovascular hemodynamic effect. Finally, we plan to test the hypothesis that the regulation of release and/or the cardiovascular actions of ANF are abnormal in human essential hypertension. The significance of these studies is that they will test the theory that ANF functions as a volume-regulatory hormone in human subjects, and that its cardiovascular actions are important to systemic and local vascular responsiveness. Secondly, these studies will determine whether the disordered volume regulation and altered vascular tone found in hypertension is due to abnormalities in the control of ANF release and/or in the actions of ANF.

心房钠尿因子（ANF）是一种多肽激素， 表现出有效的利钠、利尿和血管平滑肌作用- 放松的动作。 动物研究表明机械或 容量引起的心房舒张、钠负荷和血管加压药 激动剂刺激 ANF 的释放。 推注输注会导致 利尿之前血压短暂下降 ANF 刺激尿钠排泄。 总体而言，动物研究 表明 ANF 在体内发挥着体积调节激素的作用 与抗利尿激素和醛固酮的作用相协调。 迄今为止，ANF 的人体研究表明，ANF 具有利尿和 单次推注 ANF 的利尿钠作用，无 研究调节释放的机制和刺激 ANF。 在我们的初步研究中，高盐饮食促进了 体重增加相关的血浆 ANF 浓度增加。 直立姿势会导致血浆 ANF 下降，这表明 右侧充盈压力调节 ANF 释放。 在心脏方面 导管插入术研究发现血浆显着增加 右心房 ANF 浓度和 ANF 水平 与心房压力呈正相关。 腿部抬高 心房压力增加并刺激分泌增加 ANF 穿过心脏的速率。 总而言之，我们的研究支持 假设 ANF 可能在人类体内发挥体积作用 血浆浓度受调节的调节激素 心房压力。 本提案中概述的研究旨在 1) 确定 调节生理、荷尔蒙和容量的刺激 人血浆 ANF 浓度，2) 表征 ANF 对正常受试者的心血管作用，以及 3) 阐明 ANF 的生理调节和心血管作用 原发性高血压患者。 我们计划系统地 操纵心房压力，测试一系列血管活性激动剂 并操纵血浆容量和渗透压来确定 这些刺激中的每一个对血浆调节的贡献 ANF 浓度。 其次，采用推注和持续输注 合成 ANF 我们将测定其心血管血流动力学 影响。 最后，我们计划检验监管的假设 ANF 的释放和/或心血管作用异常 在人类原发性高血压中。 这些研究的意义在于它们将检验理论 ANF 在人体中起到体积调节激素的作用 受试者，并且其心血管作用对于 全身和局部血管反应性。 其次，这些 研究将确定音量调节是否紊乱 高血压中发现的血管张力改变是由于 ANF 释放控制和/或行为异常 的 ANF。