CARDIOVASCULAR PHARMACOLOGY OF ATRIAL NATRIURETIC FACTOR

心房利钠因子（ANF）是一种多肽激素， 具有强效的利钠利尿和血管平滑肌功能 放松的动作。 动物研究表明，机械或 容量诱导的心房牵张、钠负荷和血管加压药 激动剂刺激ANF的释放。 大剂量输注导致 在利尿之前血压短暂下降， 由ANF刺激的尿钠排泄。 总的来说，动物研究 提示ANF作为一种体积调节激素， 与抗利尿激素和醛固酮的作用一致。 迄今为止，ANF的人体研究显示利尿剂和 单次推注ANF的利钠作用，无 研究调节释放的机制和刺激， 胜利阵线。 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。 直立姿势引起血浆ANF下降，表明 右侧填充压力调节ANF释放。 心脏 导管插入术研究发现， 右心房心钠素浓度和心钠素水平 与心房压力呈正相关。 腿抬高 增加心房压力并刺激分泌增加 心钠素通过心脏的速率 总之，我们的研究支持 假设ANF可能在人体中起体积作用- 一种调节激素，其血浆浓度受 心房压 本提案中概述的研究旨在1）确定 调节的生理、激素和音量刺激 人血浆ANF浓度，2）表征 心血管活动的心钠素在正常人，和3）阐明 心钠素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 控制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，以确定 这些刺激中的每一种对血浆调节的贡献 ANF浓度。 第二，使用大剂量和持续输注 我们将测定合成ANF的心血管血流动力学 效果 最后，我们计划测试的假设，该条例 ANF的释放和/或心血管作用异常 人类原发性高血压。 这些研究的意义在于，它们将检验这一理论 ANF在人体内作为一种体积调节激素发挥作用， 受试者，其心血管作用对 全身和局部血管反应性。 其次，这些 研究将确定紊乱的音量调节是否 高血压中血管张力的改变是由于 ANF释放控制和/或 ANF的。

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.