ATRIAL NATRIURETIC PEPTIDE AND PULMONARY AIR DYNAMICS

心房钠尿肽和肺空气动力学

• 批准号: 6107051
• 负责人: MUKUL R BANERJEE
• 金额: $ 7.35万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107051
• 关键词: active sites; atrial natriuretic peptide; bronchomotion; cyclic GMP; endopeptidases; enzyme activity; enzyme inhibitors; laboratory rat; lung; micromanipulator; neprilysin; respiratory airflow disorder; respiratory epithelium; respiratory function; respiratory muscles; second messengers; vasodilators

The overall objective of this project is to investigate the role of Atrial Natriuretic Peptide (ANP) in the lung. ANP is an endogenous cardiac hormone which is released by distension of the heart and is known to relax the smooth muscles of the blood vessels in addition to its natriuretic and diuretic properties. Thus, ANP appears to be an important regulator of blood pressure. However, the presence of a large amount of ANP has been demonstrated in the lung. An increase in plasma ANP levels has also been observed in several pulmonary pathological conditions. Yet, little is known about the function of ANP in the lung, particularly regarding its ability to relax the smooth muscles of the airways. The hypotheses to be tested are: 1) ANP works on the airways without the intervention or interaction of systemic mediators or the influence of the centrally mediated reflexes, 2) Airway epithelium, particularly by its action of the neutral endopeptidases, modifies the effect of ANP on the lung, 3) ANP acts directly on the smooth muscle cells of the airways and not through the release of other intermediary compounds, 4) ANP acts on the airways through cGMP as a second messenger, and 5) ANP acts primarily on the central airways rather than on the peripheral airways. The specific aims are l) To study the action and potency of ANP in isolated-perfused lungs where the airway responses have been altered by bronchoactive agents. 2) To study the role of airway epithelium, particularly its neutral endopeptidases, on the action of ANP on lung mechanics. 3) To study the role of endothelial derived relaxing factor (EDRF) and cyclooxygenase inhibitors on the action of ANP on lung mechanics. 4) To determine if ANP acts on the airways through cGMP as the second messenger. 5) To determine the site of action of ANP within the airways. The proposed research is significant in that by establishing how ANP regulates bronchodilation it may lead to new therapies particularly for conditions of combined atrial stretch and airway dysfunction such as cardiac asthma, congestive heart failure and cor pulmonale associated with chronic obstructive pulmonary diseases.

本项目的总体目标是调查 心房利钠肽（ANP）在肺部。 ANP是一种内源性 心脏激素，由心脏扩张释放， 已知除了放松血管的平滑肌， 它的利钠利尿特性因此，ANP似乎是一种 血压的重要调节器。然而，大量的 大量的心钠素已被证明在肺。血浆浓度升高 还在几种肺病理性疾病中观察到ANP水平。 条件然而，关于ANP在肺中的功能知之甚少， 特别是关于其放松血管平滑肌的能力， 航空公司. 待检验的假设是：1）ANP作用于气道， 系统介质的干预或相互作用或影响 中枢介导反射，2）气道上皮，特别是 通过中性内肽酶的作用， 3）ANP直接作用于肺的平滑肌细胞， 而不是通过释放其他中间化合物， 4)ANP通过cGMP作为第二信使作用于气道，以及5） ANP主要作用于中央气道而不是外周气道 航空公司. 具体目标是：1）研究ANP在 其中气道反应已经改变的隔离灌注肺 支气管活性剂。2)为了研究气道上皮的作用， 尤其是中性内肽酶对ANP肺保护作用的影响 力学3)目的：探讨内皮源性舒张因子（endothelial derived relaxing factor，ERF）在血管紧张素Ⅱ（Ang Ⅱ） （EDRF）和环氧合酶抑制剂对ANP肺作用的影响 力学4)为了确定ANP是否通过cGMP作用于气道， 第二信使5)为了确定ANP的作用部位， 呼吸道该研究的意义在于， 确定ANP如何调节支气管扩张， 特别是用于心房牵张和 气道功能障碍，如心脏性哮喘、充血性心力衰竭和 肺心病合并慢性阻塞性肺疾病。